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Rechallenge With BRAF and anti-EGFR Inhibitors in Patients With Metastatic Colorectal Cancer Harboring BRAFV600E Mutation Who Progressed on Cetuximab and Encorafenib With or Without Binimetinib: A Case Series

  • Jingran Ji
    Affiliations
    Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA
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  • Chongkai Wang
    Affiliations
    Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA
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  • Marwan Fakih
    Correspondence
    Address for correspondence: Marwan Fakih, MD, Medical Oncology and Therapeutics Research, Judy and Bernard Briskin Distinguished Director of Clinical Research, Briskin Center for Clinical Research, GI Medical Oncology, City of Hope Comprehensive Cancer Center, Pavillion, Room 3208, 1500 E Duarte St, Duarte, CA 91010
    Affiliations
    Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA
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Published:December 31, 2021DOI:https://doi.org/10.1016/j.clcc.2021.12.001
      BRAFV600E is the driver mutation for approximately 10% of colorectal cancers and is found more often in right-sided disease and older patients.
      • Yaeger R
      • Chatila WK
      • Lipsyc MD
      • et al.
      Clinical sequencing defines the genomic landscape of metastatic colorectal cancer.
      • Davies H
      • Bignell GR
      • Cox C
      • et al.
      Mutations of the BRAF gene in human cancer.
      • Tie J
      • Gibbs P
      • Lipton L
      • et al.
      Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation.
      The presence of this mutation is associated with a poor prognosis and resistance to chemotherapy, especially in the metastatic setting.
      • De Roock W
      • Claes B
      • Bernasconi D
      • et al.
      Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.
      • Loupakis F
      • Ruzzo A
      • Cremolini C
      • et al.
      KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer.
      • Clarke CN
      • Kopetz ES.
      BRAF mutant colorectal cancer as a distinct subset of colorectal cancer: clinical characteristics, clinical behavior, and response to targeted therapies.
      Standard first line therapy in these patients has a significantly shorter overall survival compared to patients with BRAF wild-type disease.
      • Loupakis F
      • Cremolini C
      • Masi G
      • et al.
      Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer.
      ,
      • Cremolini C
      • Loupakis F
      • Antoniotti C
      • et al.
      FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study.
      Historically, subsequent lines of chemotherapy have shown limited efficacy with median progression free survival (PFS) of 2 to 3 months and overall survival (OS) of around 4 to 6 months.
      • Morris V
      • Overman MJ
      • Jiang ZQ
      • et al.
      Progression-free survival remains poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer.
      ,
      • Mitani S
      • Taniguchi H
      • Honda K
      • et al.
      Analysis of efficacy and prognostic factors in second-line chemotherapy for BRAF V600E mutant metastatic colorectal cancer.
      The addition of an EGFR tyrosine kinase inhibitor to the therapeutic regimen did not have any benefit in PFS or OS.
      • Seymour MT
      • Brown SR
      • Middleton G
      • et al.
      Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial.
      ,
      • Peeters M
      • Oliner KS
      • Price TJ
      • et al.
      Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer.

      Keywords

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