Biomarker |
Gene |
Drug | Tumor Type | Response Description of the effect the treatment has when the tumor is characterized by the specified biomarker | Evidence level Kind of experiment from which the evidence supports the described biomarker | Source Reference supporting the evidenced association | Statement Interpretation or report about the evidenced association |
|---|---|---|---|---|---|---|---|
| biomarker | gene | drug | tumor | response | evidence | source | statement |
| AKT1 E17K |
AKT1 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Both patients with AKT1 E17K alone had primary resistance to cetuximab, whereas 7 of 8 patients with PIK3CA mutation alone experienced tumor shrinkage or stability with anti-EGFR therapy. Thus, AKT1 E17K mutations contribute to primary resistance to cetuximab and serve as an actionable alteration. |
| AKT1 E17K, BRAF WILD TYPE, KRAS WILD TYPE |
AKT1 BRAF KRAS |
Cetuximab, Irinotecan | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, 100% (2/2) colorectal carcinoma patients harboring an AKT1 E17K mutation and wild-type KRAS/BRAF demonstrated resistance to Erbitux (cetuximab) in combination with Camptosar (irinotecan). |
| AKT2 OVEREXPRESSION |
AKT2 |
Trastuzumab | Malignant Breast Neoplasm | Sensitive | Clinical |
Publications Database: CIViC |
In HER2+ metastatic breast cancer treated with trastuzumab (n = 74 patients), the expression of AKT2 and pAkt-Thr308 and/or pAkt-Ser473 localized in nucleus+cytoplasm was associated with an improved time to progression (TTP) and overall survival (OS) compared to AKT2 negative tumors as measured by immunohistochemistry. |
| ANXA1 OVEREXPRESSION |
ANXA1 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis of a Phase III trial, ERBB2 (HER2) positive breast cancer patients with over expression of ANXA1 demonstrated a decreased survival benefit to Herceptin (trastuzumab) compared to treated ERBB2 (HER2) positive breast cancer patients with decreased expression of ANXA1. |
| ANXA1 OVEREXPRESSION, ARID1A AMPLIFICATION |
ANXA1 ARID1A |
Trastuzumab | Breast Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Loss of ARID1A Activates ANXA1, which Serves as a Predictive Biomarker for Trastuzumab Resistance. |
| ANXA1 OVEREXPRESSION, ARID1A ONCOGENIC MUTATION |
ANXA1 ARID1A |
Trastuzumab | Breast Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Loss of ARID1A Activates ANXA1, which Serves as a Predictive Biomarker for Trastuzumab Resistance. |
| ANXA11 R197C |
ANXA11 |
Bevacizumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Overall responses for bevacizumab regimens revealed that patients carrying the TT genotype at ANXA11 rs1049550 or at least one G allele at LINS1 rs11247226 seemed greater chemosensitive than those carrying at least one C allele or the AA genotype, respectively (P < 0.05). |
| ANXA11 R197C |
ANXA11 |
Bevacizumab, Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
CONCLUSION: LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed. |
| ARAF S490T |
ARAF |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Phase 1b study of vemurafenib, cetuximab and irinotecan in 19 BRAF V600E mutant colorectal cancer patients. cfDNA panel sequencing was performed in 10 patients after disease progression. One patient had an acquired ARAF S490T mutation that was not identified before treatment initiation. |
| AREG OVEREXPRESSION |
AREG |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
226 cetuximab-treated patients with colorectal cancer (CRC) were analyzed for mRNA expression (by qPCR) of EGFR and its ligands (EGF, TGFA, AREG and EREG). High AREG mRNA expression in KRAS wild type tumours was a favorable predictor in a multivariate analysis (median survival 33 vs. 15 months, p=0.0005). Cetuximab-treated patients with AREG-low KRAS wild type CRC had poor survival, similar to KRAS mutated CRC. |
| AREG OVEREXPRESSION |
AREG |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Prospectively planned retrospective biomarker study in archived tumor tissue from 323 patients from the PICCOLO trial (panitumumab plus irinotecan in CRC patients with KRAS wt). Tumors were classified as high expressor (either EREG or AREG mRNA level) or low expressor (neither EREG nor AREG in top tertile). For RAS wild-type patients with high ligand expression, median PFS was 8.3 [4.0-11.0] months (irinotecan with panitumumab) vs 4.4 [2.8-6.7] months (irinotecan alone); HR, 0.38 [95% CI, 0.24-0.61]; P < .001. In RAS wild-type patients with low ligand expression, median PFS was 3.2 [2.7-8.1] months (irinotecan with panitumumab) vs 4.0 [2.7-7.5] months (irinotecan); HR, 0.93 [95% CI, 0.64-1.37]; P = .73; interaction test results were significant [P = .01]). Results were less clear for response rate (interaction P = .17) and OS (interaction P = .11). |
| AREG OVEREXPRESSION, EREG OVEREXPRESSION |
AREG EREG |
Irinotecan, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis of a Phase I trial, RAS wild-type colorectal cancer patients over expressing AREG and EREG demonstrated a greater PFS (8.3 mo vs 4.4 mo) when treated with a combination of Camptosar (irinotecan) and Vectibix (panitumumab) compared to Camptosar (irinotecan) alone. |
| AREG UNDEREXPRESSION, EREG UNDEREXPRESSION |
AREG EREG |
Irinotecan, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a retrospective analysis of a Phase I trial, the combination of Camptosar (irinotecan) and Vectibix (panitumumab) treatment in RAS wild-type colorectal cancer patients with decreased expression of AREG and EREG resulted in a similar PFS (3.2 mo vs 4.0 mo) when compared to Camptosar (irinotecan) alone. |
| ARID1A DELETION |
ARID1A |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, ERBB2 (HER2) positive breast cancer cells with ARID1A loss demonstrated resistance to Herceptin (trastuzumab) in culture. |
| ARID1A DELETION, ERBB2 AMPLIFICATION |
ARID1A ERBB2 |
MK2206, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, a breast cancer cell line with ARID1A loss and harboring ERBB2 (HER2) amplification demonstrated restored sensitivity to Herceptin (trastuzumab) when additionally treated with MK2206 in culture. |
| ATN1 UNDEREXPRESSION, BRAF WILD TYPE, KRAS WILD TYPE |
ATN1 BRAF KRAS |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, ATN1 mRNA level was decreased in the progressive disease group compared to the disease control group in KRAS and BRAF wild-type colorectal cancer patients treated with Erbitux (cetuximab) or Vectibix (panitumumab), which supported its potential role as a predictive marker for treatment response. |
| ATN1 UNDEREXPRESSION, BRAF WILD TYPE, KRAS WILD TYPE |
ATN1 BRAF KRAS |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, ATN1 mRNA level was decreased in the progressive disease group compared to the disease control group in KRAS and BRAF wild-type colorectal cancer patients treated with Erbitux (cetuximab) or Vectibix (panitumumab), which supported its potential role as a predictive marker for treatment response. |
| BIRC5 OVEREXPRESSION |
BIRC5 |
Trastuzumab | HER2 Positive Breast Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
13 HER2 breast cancer patients were treated with trastuzumab and then trastuzumab + docetaxel prior to surgery. Pretreatment biopsies and post-treatment surgical samples were obtained, and microarray performed. 5 of 13 patients responded to treatment, and pretreatment biopsies from non-responders showed significantly higher survivin (BIRC5) mRNA (p=0.026) levels than responders. In HER2 positive, trastuzumab-sensitive BT474 cells, overexpression of survivin blunted sensitivity to trastuzumab. In HER2 positive trastuzumab-resistant breast cancer cell lines, knockdown of survivin with RNAi or with YM155 induced growth inhibition and apoptosis. |
| BRAF AMPLIFICATION |
BRAF |
Dabrafenib, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Paired pre-treatment and post-progression tumor biopsies from BRAF-mutant CRC patients treated with RAF inhibitor combinations were analyzed. Alterations in MAPK pathway genes were found in resistant tumors not present in matched pre-treatment tumors, including KRAS amplification, BRAF amplification, and a MEK1 mutation. |
| BRAF AMPLIFICATION, BRAF V600E |
BRAF |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired BRAF V600E amplification. |
| BRAF AMPLIFICATION, BRAF V600E |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF D594G |
BRAF |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 53, KRAS exon 2 wild-type, metastatic colorectal cancer patients, patients harboring BRAF G466A (n=1), G469A (n=2), D594G (n=1), or V600E (n=2) mutations were reported to be non-responders to cetuximab in combination with irinotecan, (BRAF mutation positive: responders vs. non-responders = 0 vs. 6; BRAF wild-type: responders vs. non-responders 30 vs. 17; P=0.004), as compared to patients with wild-type BRAF. |
| BRAF D594G |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Two patients with stage IV BRAF (D594G) mutations received anti-EGFR antibody therapy (cetuximab and panitumumab). The first patient was on FOLFOX plus bevacizumab and showed no signs of progression for 10 months. No response was observed after cetuximab was given as a third line therapy. The second patient received panitumumab with FOLFOX and showed no signs of progression for 8 months with reduction of the size of metastases. |
| BRAF G466V |
BRAF |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, treatment with Erbitux (cetuximab) reduced ERK signaling and resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1. |
| BRAF G466V |
BRAF |
Irinotecan, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, a patient with metastatic colorectal cancer harboring BRAF G466V, and with wild-type RAS and NF1, demonstrated tumor regression following treatment with Vectibix (panitumumab) plus Camptosar (irinotecan). |
| BRAF G596V, NRAS G13R |
BRAF NRAS |
Cetuximab, LSN3074753 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in a patient-derived xenograft model of colorectal cancer harboring BRAF G596V and NRAS G13R. |
| BRAF MUTATION |
BRAF |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks. |
| BRAF MUTATION |
BRAF |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed a response to cetuximab whereas 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. |
| BRAF MUTATION |
BRAF |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks. |
| BRAF MUTATION |
BRAF |
Cetuximab, LSN3074753 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12). |
| BRAF MUTATION |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
A quantitative synthesis was performed on nine studies comparing treatment of metastatic colorectal cancer with cetuximab or panitumumab and chemotherapy, versus chemotherapy alone, or with other targeted inhibitors. It was found that in the patient subgroup with BRAF mutation (V600E in the majority of cases), there were no benefits to overall survival, progression free survival, or overall response rate with addition of cetuximab or panitumumab to treatment. This conclusion held in the first line treatment as well as general treatment setting. |
| BRAF MUTATION |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer. |
| BRAF NON-V600E MUTATION |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort. The median PFS in BRAF(non-V600E) mutations was 2.4 months, similar to that in RAS or BRAF(V600E) mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months). Although BRAF(non-V600E) mutations identified were a rare and unestablished molecular subtype, certain BRAF(non-V600E) mutations might contribute to a lesser benefit of anti-EGFR monoclonal antibody treatment. |
| BRAF V600 |
BRAF |
Alpelisib (BYL719), Dabrafenib, Panitumumab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
These results indicate that combination treatment of encorafenib and cetuximab ± BYL719 is well tolerated with promising antitumor activity in pts with advanced BRAFm CRC who failed standard treatment. |
| BRAF V600 |
BRAF |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation. |
| BRAF V600 |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Patients with BRAF-V600 mutated cancers were identified (n=122) and subsequently underwent targeted therapy. 27 patients with colorectal cancer were treated with vemurafenib and cetuximab (N=24 with BRAF V600E mutation, N=3 with V600 unknown status). One response was observed; however, approximately half the patients had tumor regression that did not meet the standard criteria for a partial response. Median progression-free survival and overall survival for patients receiving combination therapy were 3.7 months (95% CI, 1.8 to 5.1) and 7.1 months (95% CI, 4.4 to not reached), respectively. Patients were heavily pretreated, with a median of two lines of previous therapy (range, one to six). |
| BRAF V600 |
BRAF |
Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In metastatic colorectal cancer patients with wildtype KRAS, BRAF mutations were associated with poor progression free survival regardless of treatment (panitumumab with best supportive care or best supportive care alone). |
| BRAF V600E |
BRAF |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
BGB-283, Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, BGB-283 in combination with Erbitux (cetuximab) demonstrated enhanced tumor suppression in colorectal cancer cell line xenograft models harboring BRAF V600E. |
| BRAF V600E |
BRAF |
BI 882370, Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Erbitux (cetuximab) in xenograft models, resulting in tumor growth inhibition and partial tumor regression. |
| BRAF V600E |
BRAF |
Bevacizumab, Capecitabine, Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Mouse xenografts using HT29 cells harboring the BRAF V600E mutation treated with combination therapy (capecitabine, vemurafenib, bevacizumab) showed increased survival and reduced tumor burden compared to single and double agent therapies. |
| BRAF V600E |
BRAF |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| BRAF V600E |
BRAF |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
Chemotherapy-refractory patients with colorectal cancer harboring BRAF mutations had lower response and disease control rates as well as shorter progression free and overall survival following cetuximab plus chemotherapy than those with wildtype BRAF. |
| BRAF V600E |
BRAF |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In a retrospective study of 148 treatment naive metastatic colorectal cancer patients, patients with BRAF V600E (n=14) mutation treated with FOLFOX4 plus cetuximab were associated with a decreased progression free survival (7.2mo vs. 9.7mo, HR:0.39, 95% CI:0.21-0.72, P=0.0017), and decreased overall survival (11.7mo vs. 28.5mo, HR:0.23, 95% CI:0.12-0.41, P<0.0001), as compared to patients with wildtype BRAF. |
| BRAF V600E |
BRAF |
Cetuximab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Erbitux (cetuximab) is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). |
| BRAF V600E |
BRAF |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Dabrafenib, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Erlotinib, Gefitinib, Vemurafenib | Colon Carcinoma | Sensitive | Preclinical |
Publications Database: ResCur |
Inhibition of the BRAF(V600E) oncoprotein by the small-molecule drug PLX4032 (vemurafenib) is highly effective in the treatment of melanoma. Our data suggest that BRAF(V600E) mutant colon cancers (approximately 8-10% of all colon cancers), for which there are currently no targeted treatment options available, might benefit from combination therapy consisting of BRAF and EGFR inhibitors. |
| BRAF V600E |
BRAF |
Cetuximab, Gefitinib, Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
5 of 7 colorectal cancer (CRC) cell lines with BRAF V600E mutation were resistant to treatment with the BRAF inhibitor vemurafenib. An RNAi screen in the WiDr cell line (a V600E CRC line) identified EGFR as an enhancer for survival when exposed to vemurafenib. Treatment with vemurafenib and EGFR inhibitor (cetuximab or gefitinib) in V600E CRC cells (WiDr, VACO432 and KM20) showed inhibited growth as well as induction of the cleaved PARP apoptotic marker. WiDr and VACO432 cells were injected into immunodeficient mice. Modest response was seen with vemurafenib treatment, while combination treatment showed considerable tumor growth inhibition as compared to control. |
| BRAF V600E |
BRAF |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Phase 1b study of vemurafenib, cetuximab and irinotecan in 19 patients with colorectal cancer (1 with appendiceal cancer). Six of 17 evaluable patients achieved an objective response, 15 patients total had either stable disease or radiographic response (the patient with appendiceal cancer had disease progression). Estimated median PFS was 7.7 months. Effect of the combined treatment was also observed in xenograft and cell line studies. |
| BRAF V600E |
BRAF |
Cetuximab, Irinotecan, Vemurafenib | Malignant Colon Neoplasm | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Zelboraf (vemurafenib), Erbitux (cetuximab), and Camptosar (irinotecan) combination therapy is included in guidelines for advanced or metastatic colon cancer patients harboring BRAF V600E (NCCN.org). |
| BRAF V600E |
BRAF |
Cetuximab, PLX4720 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of PLX4720 and Erbitux (cetuximab) inhibited tumor growth in colorectal cancer cell line xenograft models harboring BRAF V600E. |
| BRAF V600E |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
This meta-analysis of 7 randomized control trials evaluating overall survival (OS) (8 for progression free survival) could not definitely state that survival benefit of anti-EGFR monoclonal antibodies is limited to patients with wild type BRAF. In other words, the authors believe that there is insufficient data to justify the exclusion of anti-EGFR monoclonal antibody therapy for patients with mutant BRAF. In these studies, mutant BRAF specifically meant the V600E mutation. |
| BRAF V600E |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort. The median PFS in BRAF(non-V600E) mutations was 2.4 months, similar to that in RAS or BRAF(V600E) mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months). |
| BRAF V600E |
BRAF |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In metastatic colorectal cancer patients with wildtype KRAS status, those with a BRAF V600E mutation were less likely to respond to treatment with cetuximab or panitumumab than those with wildtype BRAF (0% vs. 32% , P=0.029). Regardless of KRAS status, patients with BRAF mutations had reduced progression-free and overall survival (P=0.0107 and P <0.0001, respectively). Transfection of the colorectal cancer cell line DiFi with a BRAF V600E expression vector conferred decreased sensitivity to cetuximab and panitumumab in comparison to cells transfected with empty vector. |
| BRAF V600E |
BRAF |
Cetuximab, Panitumumab, Sorafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
The effect of the BRAF V600E mutation on cetuximab or panitumumab response was also assessed using cellular models of CRC. Treatment with the BRAF inhibitor sorafenib restored sensitivity to panitumumab or cetuximab of CRC cells carrying the V600E allele. |
| BRAF V600E |
BRAF |
Cetuximab, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Cetuximab, Sorafenib | Colon Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Sorafenib and cetuximab therapy led to a mixed radiographic response with some areas showing dramatic improvement and other areas showing stable disease over a 7-month period which is a notably long period of progression-free survival for V600E BRAF mutated colon cancer. |
| BRAF V600E |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) was tolerated and showed clinical benefit in a patient with BRAF V600E mutant colorectal cancer. |
| BRAF V600E |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Zelboraf (vemurafenib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture. |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, treatment with the combination of Vectibix (panitumumab) and Tafinlar (dabrafenib) resulted in stable disease in 7/8 colorectal cancer patients harboring a BRAF V600E mutation (J Clin Oncol 32:5s, 2014 (suppl; abstr 3515)). |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib) and Vectibix (panitumumab) resulted in an overall response rate of 10% (2/20, 1 complete response, 1 partial response), stable disease in 80% (16/20), and a median progression-free survival of 3.5 months in patients with BRAF V600E colorectal cancer. |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Efficacy and tolerability in an open-label phase I/II study of MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in combination in patients (pts) with BRAF V600E mutated colorectal cancer (CRC). P can be safely combined with D or D/T. Encouraging evidence of clinical activity has been seen.// Updated efficacy of the MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in patients (pts) with BRAF V600E mutated (BRAFm) metastatic colorectal cancer (mCRC).Encouraging clinical activity with acceptable tolerability is seen with the triplet D+T+P in BRAFm mCRC. |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in an overall response rate of 21% (19/91, 1 complete response, 18 partial response), stable disease in 65% (59/91), and a median progression-free survival of 4.2 months in patients with BRAF V600E colorectal cancer. |
| BRAF V600E |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this trial, 142 patients with metastatic, BRAF V600E mutant colorectal cancer were randomized to receive either BRAF inhibitor dabrafenib (D) + EGFR inhibitor panitumumab (P); or a triple therapy of D + P and MEK inhibition with trametinib (T) or T + P. Confirmed response rates for D+P (n=20), D+T+P (n=91), and T+P (n=31) were 10%, 21%, and 0%, respectively. |
| BRAF V600E |
BRAF |
Irinotecan, Panitumumab, Vemurafenib | Malignant Colon Neoplasm | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Zelboraf (vemurafenib), Vectibix (panitumumab), and Irinotecan combination therapy is included in guidelines for advanced or metastatic colon cancer patients harboring BRAF V600E (NCCN.org). |
| BRAF V600E |
BRAF |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.// KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer.// These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. |
| BRAF V600E |
BRAF |
Panitumumab | Malignant Colon Neoplasm | Resistant | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Vectibix (panitumumab) is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). |
| BRAF V600E |
BRAF |
Panitumumab, Sorafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Cetuximab or panitumumab may be ineffective in patients with BRAF mutation unless BRAF inhibitor such as Sorafenib is introduced. |
| BRAF V600E |
BRAF |
Panitumumab, Trametinib | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this trial, 142 patients with metastatic, BRAF V600E mutant colorectal cancer were randomized to receive either BRAF inhibitor dabrafenib (D) + EGFR inhibitor panitumumab (P); or a triple therapy of D + P and MEK inhibition with trametinib (T) or T + P. Confirmed response rates for D+P (n=20), D+T+P (n=91), and T+P (n=31) were 10%, 21%, and 0%, respectively. |
| BRAF V600E |
BRAF |
Panitumumab, Trametinib | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination therapy consisting of Vectibix (panitumumab) and Mekinist (trametinib) resulted in an overall response rate of 0% (0/31), stable disease in 55% (17/31), and a median progression-free survival of 2.6 months in patients with BRAF V600E colorectal cancer. |
| BRAF V600E |
BRAF |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Case report of a patient with BRAF V600E mutant metastatic colorectal cancer. Combined EGFR and BRAF inhibition (panitumumab and vemurafenib) showed an initial partial response for 4 months with subsequent disease progression. |
| BRAF V600E |
BRAF |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Treatment response to mutant BRAF inhibitor vemurafenib and EGFR inhibitor panitumumab was assayed in 12 patients with metastatic colorectal cancer (CRC) who had progressed on chemotherapy. Two patients had confirmed partial responses, and 2 showed stable disease over 6 months. The authors conclude that although some efficacy is seen, only a small subset of patients respond to this treatment and the responses are not durable. |
| BRAF V600E |
BRAF |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, 83% (10/12) of patients with colorectal cancer carrying a BRAF V600E mutation demonstrated tumor regression when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab). |
| BRAF V600E MSI HIGH |
BRAF |
Dabrafenib, Panitumumab, Trametinib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in improved response rate (46%, 5/11 vs 27%, 18/67) and progression-free survival (HR=2.64, p=0.0449) in BRAF V600E mutant colorectal cancer patients with MSI-high/MMR-deficient tumors, compared to patients with MSS/MMR-proficient tumors. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Dabrafenib, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Selumetinib (AZD6244), Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Selumetinib (AZD6244), and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture. |
| BRAF V600E, EGFR AMPLIFICATION |
BRAF EGFR |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture. |
| BRAF V600E, EGFR AMPLIFICATION, EGFR S492R |
BRAF EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colorectal cancer patient harboring EGFR amplification, BRAF V600E, and EGFR S492R demonstrated resistance to Erbitux (cetuximab). |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Erbitux (cetuximab) in culture. |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Cetuximab, Dabrafenib, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquired secondary resistance mutation of EGFR G465R. |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Vectibix (panitumumab) in culture. |
| BRAF V600E, EGFR G465R |
BRAF EGFR |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment in culture. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T. |
| BRAF V600E, KRAS A146T |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to combination treatment consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture, likely due to the acquisition of KRAS A146V and A146T secondary resistance mutations. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) in culture. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) in culture. |
| BRAF V600E, KRAS A146T, KRAS A146V |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS AMPLIFICATION |
BRAF KRAS |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired KRAS amplification. |
| BRAF V600E, KRAS AMPLIFICATION |
BRAF KRAS |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture. |
| BRAF V600E, KRAS AMPLIFICATION |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS G12D |
BRAF KRAS |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture. |
| BRAF V600E, KRAS G12D |
BRAF KRAS |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS G12D |
BRAF KRAS |
Cetuximab, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS G12D |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquisition of KRAS G12D. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquisition of KRAS G13D. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, SCH772984 | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and SCH772984 in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) in culture. |
| BRAF V600E, KRAS G13D |
BRAF KRAS |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture. |
| BRAF V600E, KRAS WILD TYPE |
BRAF KRAS |
Cetuximab, Irinotecan | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Also, BRAF V600E mutation has been associated with resistance. METHODS: We investigated the role of KRAS codons 61 and 146 and BRAF V600E mutations in predicting resistance to cetuximab plus irinotecan in a cohort of KRAS codons 12 and 13 wild-type patients. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Alpelisib (BYL719), Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Dabrafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Dabrafenib, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, SCH772984 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 L115P |
BRAF MAP2K1 |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture. |
| BRAF V600E, MAP2K1 V211D |
BRAF MAP2K1 |
Cetuximab, Dabrafenib, Trametinib | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture. |
| BRAF V600E, MAP2K1 V211D |
BRAF MAP2K1 |
Cetuximab, Encorafenib (LGX818) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture. |
| BRAF V600E, MAP2K1 V211D |
BRAF MAP2K1 |
Cetuximab, Selumetinib (AZD6244) | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired secondary resistant mutation of MAP2K1 V211D. |
| BRAF V600E, MDM2 AMPLIFICATION, MET AMPLIFICATION |
BRAF MDM2 MET |
Panitumumab, Vemurafenib | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical case study, a colorectal cancer patient harboring BRAF V600E, eventually developed resistance to Vectibix (panitumumab) and Zelboraf (vemurafenib) due to acquiring amplification of MET and MDM2. |
| BRAF V600E, MET AMPLIFICATION |
BRAF MET |
Panitumumab, Vemurafenib | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
MET-Driven Resistance to Dual EGFR and BRAF Blockade May Be Overcome by Switching from EGFR to MET Inhibition in BRAF-Mutated Colorectal Cancer. |
| BRAF V600E, PIK3CA P449T |
BRAF PIK3CA |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Erbitux (cetuximab) in culture. |
| BRAF V600E, PIK3CA P449T |
BRAF PIK3CA |
Cetuximab, Regorafenib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring BRAF V600E and PIK3CA P449T in culture. |
| BRAF V600E, TP53 Q192K |
BRAF TP53 |
Panitumumab, Vemurafenib | Malignant Colon Neoplasm | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colon cancer patient harboring BRAF V600E and TP53 Q192K demonstrated a partial response when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab). |
| BRAF V600X |
BRAF |
Cetuximab, Irinotecan, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib trial, the addition of Zelboraf (vemurafenib) to Camptosar (irinotecan) plus Erbitux (cetuximab) improved progression-free survival (4.4 mo vs. 2.0 mo), and disease control rate (67% vs. 22%), compared to Camptosar (irinotecan) plus Erbitux (cetuximab) without Zelboraf (vemurafenib), in patients with BRAF V600-mutant colorectal cancer (J Clin Oncol 35, 2017 (suppl 4S; abstract 520)). |
| BRAF V600X |
BRAF |
Cetuximab, Vemurafenib | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II clinical trial, treatment with the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) resulted in an overall response rate of 4% (1/26), stable disease in 69% (18/26), and a median progression-free survival of 3.7 months in patients with BRAF V600-mutant colorectal cancer. |
| BRAF WILD TYPE, KRAS WILD TYPE, NRAS WILD TYPE |
BRAF KRAS NRAS |
Bevacizumab, Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial (MACBETH), first-line treatment with the combination of Erbitux (cetuximab) and FOLFIRI, followed by Avastin (bevacizumab) maintenance, demonstrated activity in BRAF/KRAS/NRAS wild-type metastatic colorectal cancer patients, resulting in a median overall survival in the intent-to-treat population of 32.2 mo and response rate of 75% (43/57), however, resulted in a 10-mo PFS rate of 40.4% (23/57), which did not meet the primary endpoint of 70%. |
| BRAF WILD TYPE, KRAS WILD TYPE, NRAS WILD TYPE |
BRAF KRAS NRAS |
Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial (MACBETH), first-line treatment with the combination of Erbitux (cetuximab) and FOLFIRI, followed by Erbitux (cetuximab) maintenance, demonstrated activity in BRAF/KRAS/NRAS wild-type metastatic colorectal cancer patients, resulting in a median overall survival in the intent-to-treat population of 33.2 mo and response rate of 68% (40/59), however, resulted in a 10-mo PFS rate of 50.8% (30/59), which did not meet the primary endpoint of 70%. |
| BRAF WILD TYPE, KRAS WILD TYPE, NRAS WILD TYPE, PIK3CA WILD TYPE |
BRAF KRAS NRAS PIK3CA |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) inhibited growth of human colorectal cancer cells wild-type for BRAF, KRAS, NRAS and PIK3CA in culture. |
| BRAF WILD TYPE, KRAS WILD TYPE, NRAS WILD TYPE, PIK3CA WILD TYPE |
BRAF KRAS NRAS PIK3CA |
Cetuximab, FOLFOX | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial, Erbitux (cetuximab) in combination with FOLFOX resulted in improved median progression-free survival (6.9 months) comparing to FOLFOX alone (5.3 months) in BRAF, KRAS, NRAS, and PIK3CA wild-type colorectal cancer patients (hazard ratio =0.56). |
| BRAF WILD TYPE, KRAS WILD TYPE, PIK3CA MUTATION |
BRAF KRAS PIK3CA |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a retrospective study, Erbitux (cetuximab) treatment, alone or in combination, resulted in disease regression or stable disease in 88% (7/8) KRAS/BRAF-wild type colorectal carcinoma patients harboring a PIK3CA mutation. |
| CCND1 OVEREXPRESSION |
CCND1 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, treatment with Herceptin (trastuzumab) resulted in a decreased response in ERBB2 (HER2) receptor positive breast cancer cells with induced overexpression of CCND1 in culture. |
| EGFR AMPLIFICATION |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
87 patients with metastatic colorectal cancer treated with cetuximab were retrospectively analyzed for EGFR amplifications by FISH. In multivariate analysis, EGFR amplification predicted response and overall survival independent of KRAS status. |
| EGFR AMPLIFICATION |
EGFR |
Cetuximab, Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this meta-analysis (14 studies, 1021 patients), EGFR gene copy number (GCN) was predictive of improved progression free survival (PFS) and overall survival (OS) with cetuximab or panitumumab regardless of KRAS status. For the pooled analysis, the objective response rate (ORR) was 65.2% (167/256) in patients with high EFGR GCN, while in patients with low EFGR GCN, the pooled ORR was 12.2% (44/361). The odds ratio (OR) was 6.905 (95% CI: 4.489-10.620; Z=8.79, P=0.000). In wild type KRAS patients, the pooled OR was 8.133 (95% CI: 4.316-15.326; Z=6.48, P=0.000). |
| EGFR AMPLIFICATION |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III study, response to Vectibix (pantitumumab) was associated with EGFR amplification in colorectal cancer patients. |
| EGFR AMPLIFICATION, EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colorectal cancer patient harboring EGFR amplification and EGFR S492R demonstrated resistance to Erbitux (cetuximab). |
| EGFR AMPLIFICATION, EGFR S492R |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a clinical study, a colorectal cancer patient harboring both EGFR amplification and EGFR S492R demonstrated a 50% tumor reduction when treated with Vectibix (panitumumab). |
| EGFR EXPRESSION |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
57 patients with chemorefractory colorectal cancer expressing EGFR (IHC staining) were treated with single-agent cetuximab in this phase 2 study. Five patients (9%; 95% CI, 3% to 19%) achieved a partial response. Twenty-one additional patients had stable disease or minor responses. The median survival in these previously treated patients with chemotherapy-refractory colorectal cancer was 6.4 months. |
| EGFR EXPRESSION |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Patients with refractory colorectal cancer expressing immunohistochemically detectable EGFR were randomly assigned to receive treatment with cetuximab (n=287) or receive supportive care alone (n=285). Patients receiving cetuximab had increased overall survival (HR=0.77, 95%CI 0.64-0.92; p=0.005), increased progression-free survival (HR=0.68, 95%CI 0.57-0.80; p<0.001), and improved quality of life at 4 months measured by survey on physical deterioration (-5.9 vs -12.5; p=0.03) and global health status (-3.6 vs. -15.2; p<0.001). |
| EGFR EXPRESSION |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
463 patients with 1% or more EGFR tumor cell membrane staining, with metastatic CRC progressive after standard chemotherapy were randomized to panitumumab plus best supportive care (BSC, n = 231) or BSC alone (n = 232). Panitumumab significantly prolonged PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66, [P < .0001]). Objective response rates favored panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10% for panitumumab and 0% for BSC (P < .0001). No difference was observed in OS (HR, 1.00; 95% CI, 0.82 to 1.22), but 76% of BSC patients entered the cross-over study. |
| EGFR EXPRESSION, KRAS WILD TYPE |
EGFR KRAS |
Cetuximab, FOLFIRI Regimen | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial that supported FDA approval, the combination of Erbitux (cetuximab) and FOLFIRI resulted in a greater tumor response rate in EGFR positive, KRAS wild-type colorectal cancer patients (59% (102/172)) compared to EGFR positive, KRAS mutant colorectal cancer patients (36.2% (38/105)). |
| EGFR G465E |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR G465E were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR G465E |
EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR G465E were resistant to Vectibix (panitumumab)-induced growth inhibition in culture. |
| EGFR G465R |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Epidermal growth factor receptor mutation mediates cross-resistance to panitumumab and cetuximab in gastrointestinal cancer.// Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.// Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR. |
| EGFR G465R |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Preclinical |
Publications Database: CGI |
Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. |
| EGFR G465R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Mutational profiling of cetuximab-resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR alleles: S464L, G465R, and I491M. |
| EGFR G465R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR G465R were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR G465R |
EGFR |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
An EGFR G465R mutation (22% of mutant alleles) was detected in a biopsy from one patient which had been previously treated with cetuximab in the analysis of 15 patients with refractory, metastatic CRC after cetuximab/panitumumab, prior to Sym004 treatment. Treatment of this patient with Sym004 yielded disease stabilization lasting 15 weeks. Sym004 is a 1:1 mixture of two non-overlapping anti-EGFR monoclonal antibodies. In vitro analysis in the murine fibroblast cell line NIH3T3 with ectopic expression of EGFR mutations S492R, R451C, K467T, and G465R showed that Sym004 effectively bound to all mutants, whereas cetuximab and panitumumab did not effectively bind to all mutants. In-vitro, Sym004 inhibited growth of S492R and G465R EGFR mutant cell lines. In-vivo analysis of S492R and G465R mutant cell lines showed regression of S492R and tumor growth delay of G465R mutant cell lines. G465R mutant cell lines were resistant to treatment with panitumumab or cetuximab in-vitro. |
| EGFR G465R |
EGFR |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Epidermal growth factor receptor mutation mediates cross-resistance to panitumumab and cetuximab in gastrointestinal cancer. |
| EGFR G465R |
EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR G465R were resistant to Vectibix (panitumumab)-induced growth inhibition in culture. |
| EGFR G719S |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: ResCur |
CONCLUSION: The colon-cancer derived G719S and G724S mutants are oncogenic and sensitive in vitro to cetuximab. |
| EGFR G719S |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Whole genome sequencing of a case of colon carcinoma revealed a G724S mutation in the EGFR gene. In-vitro, this mutation was shown to be oncogenic and sensitive to Cetuximab, yet relatively insensitive towards small molecules. The same in-vitro results could be reproduced for the G719S mutation. |
| EGFR G724S |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab. We show that G724S mutant EGFR is oncogenic and that it differs from classic lung cancer derived EGFR mutants in that it is cetuximab responsive in vitro, yet relatively insensitive to small molecule kinase inhibitors. CONCLUSION: The colon-cancer derived G719S and G724S mutants are oncogenic and sensitive in vitro to cetuximab. |
| EGFR G724S |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
Whole genome sequencing of a case of colon carcinoma revealed a G724S mutation in the EGFR gene. In-vitro, this mutation was shown to be oncogenic and sensitive to Cetuximab, yet relatively insensitive towards small molecules. |
| EGFR I491M |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Preclinical |
Publications Database: CGI |
Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. |
| EGFR I491M |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR I491M were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR I491M |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Mutational profiling of cetuximab-resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR alleles: S464L, G465R, and I491M. |
| EGFR I491M |
EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR I491M were resistant to Vectibix (panitumumab)-induced growth inhibition in culture. |
| EGFR K467T |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.// Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR. |
| EGFR K467T |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
In this preclinical study on the effects of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. In NIH3T3 cells expressing EGFR with a K467T mutation, Sym004 and panitumumab bound the mutated receptor and inhibited EGFR phosphorylation in the presence of ligand while cetuximab neither bound to nor inhibited EGFR phosphorylation of the mutated receptor. |
| EGFR K467T |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR K467T were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR K467T |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Vectibix (panitumumab) inhibited survival of colorectal cancer cell lines over expressing EGFR K467T in culture. |
| EGFR K467T |
EGFR |
Panitumumab, Sym004 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In this preclinical study on the effects of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. In NIH3T3 cells expressing EGFR with a K467T mutation, Sym004 and panitumumab bound the mutated receptor and inhibited EGFR phosphorylation in the presence of ligand while cetuximab neither bound to nor inhibited EGFR phosphorylation of the mutated receptor. |
| EGFR OVEREXPRESSION |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| EGFR OVEREXPRESSION |
EGFR |
Panitumumab | Colorectal Adenocarcinoma | Resistant | Guidelines |
FDA Guidelines Database: CGI |
- |
| EGFR R451C |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.// Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR. |
| EGFR R451C |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Erbitux (cetuximab) inhibited survival of colorectal cancer cell lines over expressing EGFR R451C in culture. |
| EGFR R451C |
EGFR |
Cetuximab, Panitumumab, Sym004 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In this preclinical study on the effects of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. The R451C mutation showed moderate drug-receptor binding with sym004, cetuximab and panitumumab treatment and inhibition of EGFR phosphorylation. |
| EGFR R451C |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Vectibix (panitumumab) inhibited survival of colorectal cancer cell lines over expressing EGFR R451C in culture. |
| EGFR R521K |
EGFR |
Cetuximab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
Allele Frequencies of the Epidermal Growth Factor Receptors Polymorphism R521K in Colorectal Cancer Patients and Healthy Subjects Indicate a Risk-Reducing Effect of K521 in Syrian Population. Studies showed the polymorphism [R521K] G A in the EGFR gene to be involved in both colorectal cancer susceptibility and clinical response to therapeutics (e.g., Cetuximab). |
| EGFR S464L |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Preclinical |
Publications Database: CGI |
Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. |
| EGFR S464L |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR S464L were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR S464L |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Mutational profiling of cetuximab-resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR alleles: S464L, G465R, and I491M. |
| EGFR S464L |
EGFR |
Panitumumab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR S464L were resistant to Vectibix (panitumumab)-induced growth inhibition in culture. |
| EGFR S468R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
Extracellular S468R mutation of the epidermal growth factor receptor (EGFR) was recently identified as the cause of resistance to cetuximab, a widely used drug in colorectal cancer treatment. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Adenocarcinoma | Resistant | Clinical |
Publications Database: CGI |
Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer.// Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.// Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. ©2016 AACR. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
In-vitro studies found this mutation to confer resistance to cetuximab. 2 of 10 patients studied also harbored EGFR S492R and were resistant to cetuximab therapy. Panitumumab was still active in-vitro and in one patient. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: CIViC |
In this preclinical study of the effects of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. The S492R mutation was sensitive to Sym004 and panitumumab treatment but resistant to cetuximab. Experiments include flow cytometry binding assay, kinase phosphorylation, cell viability, downstream signalling. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
We describe an acquired EGFR ectodomain mutation (S492R) that prevents cetuximab binding and confers resistance to cetuximab. A subject with cetuximab resistance harboring the S492R mutation responded to treatment with panitumumab. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: ResCur |
MET gene amplification emerged in 1 patient during Sym004 treatment, and a partial response was seen in a patient with EGFR(S492R) mutation that is predictive of cetuximab resistance. MET gene amplification emerged in 1 patient during Sym004 treatment, and a partial response was seen in a patient with EGFR(S492R) mutation that is predictive of cetuximab resistance. |
| EGFR S492R |
EGFR |
Cetuximab | Colorectal Carcinoma | Resistant | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, colorectal cancer cell lines over expressing EGFR S492R were resistant to Erbitux (cetuximab)-induced growth inhibition in culture. |
| EGFR S492R |
EGFR |
Panitumumab | Colorectal Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer. |
| EGFR S492R |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, Vectibix (panitumumab) inhibited survival of colorectal cancer cell lines over expressing EGFR S492R in culture. |
| EGFR S492R |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Tumor sequencing in pre- and post-therapy specimens from ten individuals with mCRC who experienced disease progression after a prior response to cetuximab with chemotherapy was performed. The S492R mutation was identified in two persons. One of them had already died, the other received treatment with panitumumab and had a partial response (50% tumor reduction in all liver lesions) for 5 months. |
| EGFR S492R |
EGFR |
Panitumumab | Colorectal Carcinoma | Sensitive | Clinical |
Publications Database: ResCur |
We describe an acquired EGFR ectodomain mutation (S492R) that prevents cetuximab binding and confers resistance to cetuximab. A subject with cetuximab resistance harboring the S492R mutation responded to treatment with panitumumab. |
| EGFR S492R |
EGFR |
Panitumumab, Sym004 | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In this preclinical study of cetuximab, panitumumab or sym004 on various EGFR mutations in colorectal cancer. The S492R mutation was sensitive to Sym004 and panitumumab treatment but resistant to cetuximab. Experiments include flow cytometry binding assay, kinase phosphorylation, cell viability, downstream signalling. |
| EPHB4 OVEREXPRESSION |
EPHB4 |
Bevacizumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
EPHB4 expression, as assessed by quantitative RT-PCR in 13 colorectal cancer patients treated with bevacizumab, was higher in non-responders (p = 0.048). No difference was observed in a control group without bevacizumab treatment. qRT-PCR results were also shown to correlate with protein expression measured by IHC. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Afatinib, Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this phase 2 trial, treatment-naive, ERBB2-positive (by IHC) breast cancer patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to afatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). The primary end point was objective response rate. Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatment of HER2-positive breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Afatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I clinical trial, ERBB2 (HER2)-positive breast cancer patients treated with Gilotrif (afatinib), in combination with Herceptin (trastuzumab), demonstrated an overall objective response rate of 11% (2/18) while 28% (5/18) attained a best response of stable disease. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Afatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
Trastuzumab resistance is thought to consist of multiple compensatory mechanisms involving ErbB family members such as increased signaling through ErbB family heterodimers. The irreversible TKI afatinib blocks EGFR, HER2, ErbB3 and ErbB4. Thus afatinib was studied in this Phase I trial of trastuzumab-progressed HER2 positive metastatic BC (MBC) in combination with continued trastuzumab treatment, where trastuzumab is still the perferred treatment for trastuzumab-progressed MBC. Objective response and disease control rates were 11% and 39%. The authors conclude that the clinical activity observed in this trial warrants further work with afatinib and trastuzumab combination therapy. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Buparlisib (BKM-120), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I clinical trial, the combination of Buparlisib (BKM120) and Herceptin (trastuzumab) was well tolerated in patients with ERBB2 (HER2)-positive advanced or metastatic breast cancer that had progressed on Herceptin (trastuzumab). |
| ERBB2 AMPLIFICATION |
ERBB2 |
CDX-3379, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Herceptin (trastuzumab) and CDX-3379 (KTN3379) inhibited tumor growth in xenograft models of ERBB2 (HER2)-amplified breast cancer, with increased efficacy compared to KTN3379 alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Capecitabine, Cetuximab, Oxaliplatin | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
141 patients were analyzed for ERBB2 (HER2) positivity by FISH and/or IHC. Only 6 (4.3%) were ERBB2 positive. These patients did not show a difference in outcome after capecitabine, oxaliplatin and chemoradiotherapy, with or without cetuximab. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Capecitabine, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In Phase II clinical trials, the combination of Xeloda (capecitabine) and Herceptin (trastuzumab) demonstrated efficacy with a manageable toxicity profile in heavily pretreated patients with ERBB2 (HER2)-positive advanced breast cancer and earlier Herceptin (trastuzumab) exposure. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Capecitabine, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In this Phase III trial, trastuzumab-based treatment was assessed in women with locally advanced or metastatic HER2 positive breast cancer who had progressed on trastuzumab. Patients had 12 weeks or greater previous trastuzumab treatment with time since end of last cycle less than 6 weeks. Primary endpoint was time to progression. 78 patients were assigned to each group, with median time to progression of 5.6 months in capecitabine group and 8.2 months in trastuzumab plus capecitabine group. The results are in contrast to the principle of change of treatment on disease progression, and authors suggest that chemotherapy-sensitizing mechanisms of trastuzumab remain intact in HER2 breast cancer cells with trastuzumab progression. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Capecitabine, Trastuzumab, Tucatinib (ARRY-380) | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib trial, the combination of Tucatinib (ARRY-380), Herceptin (trastuzumab), and Capecitabine demonstrated clinical activity in CNS metastases in patients with ERBB2 (HER2)-positive metastatic breast cancer, with 50% (1/2) of evaluable patients achieving CNS partial response and 50% (1/2) achieving CNS stable disease (San Antonio Breast Cancer Symposium 2015, Abstract P4-14-19). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Carboplatin, Docetaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) plus Perjeta (pertuzumab) therapy, is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Carboplatin, Docetaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Taxotere (docetaxel), Paraplatin (carboplatin), and Herceptin (trastuzumab) therapy is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed resistance whereas 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. Among 11 quadruple-negative samples with resistance to cetuximab, HER2 overexpression and amplification (N=3) and amplification (N=1) were identified. In an independent second retrospective cohort, 3 out of 17 patients with KRAS wt, cetuximab resitant CRC were found to harbor HER2 overexpression and amplification. In this cohort no HER2 overexpression or amplification was identified in 14 KRAS wt patients with response to cetuximab. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: JAX-CKB |
In a clinical study, ERBB2 (HER2) amplification was associated with resistance to Erbitux (cetuximab) in colorectal cancer patients. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
We identified 142 patients with metastatic colorectal cancer whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF. All patients received cetuximab after oxaliplatin, irinotecan, and fluoropyrimidine failure. HER2 status was determined using immunohistochemistry and silver in situ hybridization and correlated with cetuximab efficacy. Of 142 RAS and BRAF wild-type tumors, we observed 7 cases (4.9%) of HER2 amplification by SISH. After a median follow-up of 13.2 months (range, 1.4-78.1 months), median progression-free survival (PFS) was significantly different according to HER2 status: 3.1 months in patients with HER2 amplification compared with 5.6 months in those with non-amplified HER2 (HR = 2.73; 95% CI = 1.18-6.31; P = 0.019). Overall survival (OS) was not significantly different between groups, although there was a tendency towards shorter OS in patients with HER2-amplified tumors (HR = 0.31; 95% CI = 0.61-2.82; 10.1 vs. 13.5 months; P = 0.488). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xenografts harboring KRAS (N=18), NRAS (N=7) or BRAF (N=3) mutations showed a response to cetuximab whereas 1 out of 4 xenografts with a PIK3CA mutation responded to cetuximab. Among 11 quadruple-negative samples with resistance to cetuximab, HER2 overexpression and amplification (N=3) and amplification (N=1) were identified. In an independent second retrospective patient cohort, 3 out of 17 patients with KRAS wt, cetuximab resitant CRC were found to harbor HER2 overexpression and amplification. In this cohort no HER2 overexpression or amplification was identified in 14 KRAS wt patients with response to cetuximab. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab, Lapatinib | Colorectal Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Erbitux (cetuximab) and Tykerb (lapatinib) induced tumor regression in patient-derived xenograft (PDX) models of colorectal cancer with ERBB2 (HER2) amplification. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cetuximab, Panitumumab | Colorectal Carcinoma | Resistant | Clinical |
Publications Database: CIViC |
HER2 amplification (FISH) was assessed in 170 KRAS wt mCRC patients treated with cetuximab or panitumumab. HER2 copy number status was significantly correlated with respoinse rate, PFS and OS. Patients with amplification in all neoplastic cells (4%) had worse outcome compared to patients without amplification (35%, intermediate outcome) or amplification in minor clones (61%, highest survival probability) |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cyclophosphamide, Doxorubicin, Paclitaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab) and Perjeta (pertuzumab), is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer who are node positive (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Cyclophosphamide, Doxorubicin, Paclitaxel, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Sequential therapy, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by Taxol (paclitaxel) plus Herceptin (trastuzumab), is included in the guidelines as adjuvant therapy for patients with hormone receptor-negative (ER and PR), ERBB2 (HER2)-positive breast cancer (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Docetaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In a randomized phase 3 trial, HER2 positive metastatic breast cancer patients given first-line treatment of pertuzumab plus trastuzumb plus docetaxel experienced improved progression free survival (18.5 vs 12.4 months, P<0.001) and increased objective response rate (80.2% vs 69.3%, P=0.001) than the control group given placebo plus trastuzumab plus docetaxel. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Docetaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
CLEOPATRA (NCT00567190) was a Phase III, randomized and double-blind, placebo-controlled study of 808 patients with HER2-positive metastatic breast cancer. Patients were HER2-positive by IHC3+ or FISH, and patients who had received prior hormonal treatment or adjuvant/neo-adjuvant therapy with or without trastuzumab for longer than 12 months before randomization were also eligible. The two arms of the study were trastuzumab and docetaxel with either placebo or pertuzumab. Median PFS in the placebo arm was 12.4 months while in the petuzumab arm 18.5 months was achieved. Median OS in the control arm was 40.8 months and 56.5 months with pertuzumab. These strong results make a case for dual antibody blockade in first line treatments of HER2-positive metastatic breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Docetaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
Publications Database: JAX-CKB |
In a Phase III trial (CLEOPATRA) that supported FDA approval, treatment with Perjeta (pertuzumab), combined with Herceptin (trastuzumab) and Taxotere (docetaxel), improved median progression free survival to 18.5 months compared to 12.4 months with placebo plus Herceptin (trastuzumab) and Taxotere (docetaxel) in patients with ERBB2 (HER2)-positive metastatic breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Docetaxel, Pertuzumab, Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase Ib/II trial, Kadcyla (trastuzumab emtansine), Taxotere (docetaxel) and Perjeta (pertuzumab) combination treatment resulted in pathologic complete response in 60.3% (44/73) of patients with ERBB2 (HER2)-positive locally advanced breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Entinostat, Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase I trial, combination treatment consisted of Entinostat, Tykerb (lapatinib) and Herceptin (trastuzumab) resulted in complete response in 9% (2/22), partial response in 14% (3/22), and stable disease in 27% (6/22) of ERBB2 (HER2) positive breast cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 609)). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Everolimus, Trastuzumab, Vinorelbine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial (BOLERO-3), the combination of Afinitor (everolimus), Herceptin (trastuzumab), and Navelbine (vinorelbine) increased progression-free survival in patients with Herceptin (trastuzumab)-resistant, ERBB2 (HER2)-positive, advanced breast cancer who had prior taxane treatment. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Gimeracil (TS-1), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II clinical trial, the combination of TS-1 (S-1) and Herceptin (trastuzumab) demonstrated safety and efficacy in patients with ERBB2 (HER2)-positive metastatic breast cancer, with an overall response rate of 53.6% (15/28), and a clinical benefit rate of 75.0% (21/28). |
| ERBB2 AMPLIFICATION |
ERBB2 |
LJM716, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Herceptin (trastuzumab) and LJM716, resulting in a delay of brain lesion growth and improved survival. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In light of results showing increased PFS using mAB plus TKI in heavily pretreated patients, the efficacy of trastuzumab plus lapatinib in a neoadjuvant setting with untreated stage II or IIIA HER2 positive breast cancer was assessed. In this randomized 3 arm phase II study (CHER-LOB), patients received (A) chemotherapy plus trastuzumab, (B) chemotherapy plus lapatinib, or (C) chemotherapy plus trastuzumab and lapatinib, with pathologic complete response (pCR) as endpoint. From 121 patients, pCR rates were 25% in arm A, 26.3% in arm B, and 46.7% in arm C. The authors conclude these results support the superiority of dual-HER2 inhibition in the neoadjuvant context of HER2 positive BC. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
This Phase III trial compared the activity of lapatinib vs. trastuzumab vs. sequential trastuzumab followed by lapatinib vs. lapatinib plus trastuzumab in an adjuvant treatment setting. 8381 women were randomized to one of four treatment arms. Patients had HER2 positive non-metastatic operable BC. The primary endpoint was disease free survival. First results report that after median 4.5 year follow up, a non significant 16% improvement in DFS was seen in trastuzumab + lapatinib vs. trastuzumab alone. The results are interpreted as showing no added benefit for labatinib addition to trastuzumab in the adjuvant treatment context. This trial is ongoing but not recruiting patients (NCT00490139). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
This Phase III study (EGF104900) was motivated by preclinical and other data demonstrating synergistic activity between lapatinib and trastuzumab against HER2 positive breast cancer (BC) cells. In this study of HER2 positive metastatic BC which had progressed on trastuzumab, two arms were compared: lapatinib vs. lapatinib + trastuzumab. Progression free survival (PFS) was the primary endpoint. For 296 patients, 148 in each arm, median PFS of 8.1 weeks for lapatinib and 12.0 for combination therapy was observed (P=0.008). The authors conclude that in the context of metastatic trastuzumab-progressed HER2 positive BC, trastuzumab with lapatinib TKI addition is a favorable treatment. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial, Tykerb (lapatinib) and Herceptin (trastuzumab) combination treatment resulted in complete response in the breast in 10.6% (7/66) and minimal residual disease in 16.7% (11/66) of ERBB2-positive breast cancer patients 11 days after receiving the treatment (European Breast Cancer Conference; Mar 2016; Abstract #6LBA). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a meta-analysis of six randomized clinical trials, Tykerb (lapatinib) and Herceptin (trastuzumab) combination treatment resulted in 13% absolute improvement in pathologic complete response rate in ERBB2 (HER2)-positive breast cancer patients compared to Herceptin (trastuzumab) single treatment. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In a randomized open label phase 3 study (NCT00553358), women with HER2 positive primary breast cancer treated with lapatinib plus trasuzumab had higher rates of pathological complete responses than seen in control groups receiving either IV trastuzumab or oral lapatinib alone (combination treatment pCR rate of 51% vs 29.5% and 24.7% for trastuzumab and lapatinib alone, respectively). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Lapatinib, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: CIViC |
In-vitro studies using ERBB2 over-expressing breast cancer cell lines BT474 and SKBR3 (with ERBB2 amplification) showed apoptosis under either labatinib or trastuzumab treatment. A marked synergistic apoptotic effect under lapatinib and trastuzumab co-treatment was observed in BT474 cells, and a milder synergistic effect was observed in SKBR3 cells. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Neratinib, Pertuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Perjeta (pertuzumab) and Nerlynx (neratinib), resulting in a delay of brain lesion growth and improved survival. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Oxaliplatin, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Herceptin (trastuzumab) and Eloxatin (oxaliplatin) resulted in growth inhibition of ERBB2 (HER2)-positive breast cancer cells in culture. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Paclitaxel, Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
NCCN Guidelines Database: JAX-CKB |
Perjeta (pertuzumab), Herceptin (trastuzumab), and Taxol (paclitaxel) therapy is included in the guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-negative, ERBB2 (HER2) receptor-positive breast cancer (NCCN.org). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Palbociclib (PD0332991), Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: CIViC |
In a panel of 47 breast cancer cell lines, HER2 overexpressing cells were among those more sensitive to CDK4/6 inhibitor Palbociclib (PD0332991). In the trastuzumab sensitive cell line Bt474, palbociclib synergized with trastuzumab in growth inhibition, while in 2 trastuzumab resistant cell lines, addition of trastuzumab to palbociclib treatment resulted in increased growth inhibition over palbociclib alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Palbociclib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, the combination of Ibrance (palbociclib) and Herceptin (trastuzumab) worked synergistically to inhibit growth of ERBB2 (HER2)-amplified breast cancer cells in culture. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Pertuzumab | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 AMPLIFICATION |
ERBB2 |
Pertuzumab, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, adjuvant Herceptin (trastuzumab), Perjeta (pertuzumab), plus chemotherapy resulted in improved invasive disease-free survival compared to Herceptin (trastuzumab) plus chemotherapy in patients with Erbb2 (Her2)-positive breast cancer (J Clin Oncol 35, 2017 (suppl; abstr LBA500)). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Pertuzumab, Trastuzumab | Malignant Breast Neoplasm | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Herceptin (trastuzumab) and Perjeta (pertuzumab), resulting in a delay of brain lesion growth and improved survival. |
| ERBB2 AMPLIFICATION |
ERBB2 |
S63845, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, S63845 and Herceptin (trastuzumab) demonstrated synergy in ERBB2 (HER2)-amplified breast cancer cells in culture and in ERBB2 (HER2)-amplified breast cancer patient-derived xenograft (PDX) models, resulting in enhanced tumor growth inhibition and overall survival compared to either agent alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
S63845, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Preclinical |
Publications Database: JAX-CKB |
In a preclinical study, S63845 and Herceptin (trastuzumab) demonstrated synergy in ERBB2 (HER2)-amplified breast cancer cells in culture and in ERBB2 (HER2)-amplified breast cancer patient-derived xenograft (PDX) models, resulting in enhanced tumor growth inhibition and overall survival compared to either agent alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Sunitinib, Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase II trial, Sutent (sunitinib), in combination with Herceptin (trastuzumab), demonstrated safety and efficacy in ERBB2 (HER2) positive advanced breast cancer patients. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Tanespimycin, Trastuzumab | Breast Adenocarcinoma | Sensitive | Clinical |
Publications Database: CGI |
HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
A randomized clinical trial of 186 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved overall survival, response rate, response duration, time to progression, and time to treatment failure for patients who received trastuzumab in addition to chemotherapy (docetaxel) compared to chemotherapy alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a meta-analysis, breast cancer patients with >12 copies of ERBB2 (HER2) had a better response to Herceptin (trastuzumab) than patients with 6-12 copies of ERBB2 (HER2). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
Publications Database: CIViC |
HERA was a Phase III trial assessing application of trastuzumab in an extended adjuvant setting. Patients were HER2 positive with completely excised invasive BC, node positive or negative, and having undergone prior adjuvant or neo-adjuvant chemotherapy. In the 3 arm study patients were given trastuzumab courses of 1 year, 2 years, or untreated. At the first planned interim analysis, trastuzumab treatment for one year was compared with observation alone. A significant difference in disease-free survival was seen with 220 DFS events out of 1693 in the observation arm versus 127 DFS events out of 1694 in the 1 year trastuzumab arm. 1 year adjuvant trastuzumab is currently the standard of care. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
A randomized clinical trial of 469 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved time to disease progression, objective response rate, and duration of response for patients who received trastuzumab in addition to chemotherapy compared to chemotherapy alone. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | Breast Adenocarcinoma | Sensitive | Guidelines |
FDA Guidelines Database: CGI |
- |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: JAX-CKB |
In a Phase III trial, Kadclya (trastuzumab emtansine) demonstrated improved median progression free survival and overall survival compared to Tykerb (lapatinib) and Xeloda (capecitabine) combination treatment in patients with ERBB2 (HER2) positive breast cancer, regardless of the expression level of Erbb2 (Her2), Egfr, and Her3, or PIK3CA mutation status. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In a randomized phase II study, first line treatment of HER2-positive metastatic breast cancer with trastuzumab emtansine (T-DM1) resulted in improved progression free survival and fewer serious adverse effects when compared to treatment with combination trastuzumab plus docetaxel (HT) (median follow up 14 months, median PFS with T-DM1 14.2 vs 9.2 with HT). |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Guidelines |
Publications Database: JAX-CKB |
In a Phase III trial (EMILIA) that supported FDA approval, treatment with Kadclya (trastuzumab emtansine) improved median progression free survival (9.6 mo vs 6.4 mo) and overall survival (30.9 mo vs 25.1 mo) compared to Tykerb (lapatinib) combined with Xeloda (capecitabine) in patients with metastatic ERBB2 (HER2)-positive breast cancer. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
The EMILIA study (NCT00829166) was a Phase II trial to assess the efficacy of trastuzumab emtansine (T-DM1, n=495) in comparison to lapatinib plus capecitabine (n=496), in treatment of advanced HER2 positive breast cancer. Patients were required to have progressed on or after treatments involving trastuzumab and a taxane, and no prior exposure to lapatinib or T-DM1. Primary endpoints included independently assessed progression free survival (PFS) and safety. PFS was 9.6 months in T-DM1 group vs. 6.4 months in lapatinib plus capecitabine. Rates of adverse events of grade 3 or higher were greater with lapatinib plus capecitabine. These results, together with other trials such as TH3RESA indicate promise for T-DM1 therapy in HER2 amplification, and this will be further studied in an arm of the NCI-MATCH trial. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
The Phase III trial, TH3RESA (NCT01419197), was performed in patients with advanced HER2 breast cancer that was heavily pretreated. Patients were required to have prior exposure to trastuzumab and lapatinib as well as a taxane. This patient population has not seen many studies, responds poorly to late-line treatment with trastuzumab, and in this study was treated with trastuzumab emtansine (T-DM1, n=404) vs. physician's choice (usually trastuzumab plus chemotherapy, n=198). Results showed progression free survival was 6.2 months in T-DM1 treatment vs. 3.3 months under physician's choice, along with lower incidence of grade 3 or worse events with T-DM1. The authors conclude that their findings in this heavily pretreated population, along with findings in the EMILIA trial, indicate promise for antibody-drug conjugates. The NCI-MATCH trial with further study T-DM1 in the context of HER2 amplification. |
| ERBB2 AMPLIFICATION |
ERBB2 |
Trastuzumab Emtansine | HER2 Positive Breast Carcinoma | Sensitive | Clinical |
Publications Database: CIViC |
In the single arm Phase II study (TDM4258g) breast cancer patients who had progressed on previous anti-HER2 therapy were given transtuzumab emtansine (T-DM1), a HER2 monoclonal antibody and antimicrotubule drug conjugate. 95 trial participants with archival primary tumor were reassessed for HER2 status (positivity defined by FISH or IHC 3+), and 74 patients were confirmed for HER2 positivity and 21 were normal. Overall response rate was 33.8% (95% CI, 23.2% to 44.9%) in patients with confirmed HER2-positive tumors and 4.8% (95% CI, 1.0% to 21.8%) in HER2 normal patients. Median PFS was 8.2 months (95% CI, 4.4 months to not estimable) in patients with confirmed HER2-positive tumors and 2.6 months (95% CI, 1.4 to 3.9 months) in HER2 normal patients. |