Encorafenib plus cetuximab treatment in BRAF V600E-mutated metastatic colorectal cancer patients pre-treated with an anti-EGFR: An AGEO-GONO case series

Eur J Cancer. 2022 Jun:168:34-40. doi: 10.1016/j.ejca.2022.03.011. Epub 2022 Apr 15.


Background: Encorafenib plus cetuximab is efficient in anti-EGFR-naïve patients with BRAFV600E mutated (BRAFm) metastatic colorectal cancer (mCRC). No data are available concerning the efficacy of BRAF inhibitors associated with anti-EGFRs (B + E) in patients previously treated with an anti-EGFR agent.

Methods: We retrospectively collected a series of patients with BRAFm mCRC treated with B + E after previous anti-EGFR treatment, in 14 centers. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment, and we reported objective response and disease control rates (ORR, DCR; RECIST V1.1).

Results: Twenty-five BRAFm mCRC patients were enrolled. Prior to B + E treatment, 4/10/11 patients were treated with 1/2/> 2 previous treatment lines. Ten patients received previous panitumumab, 14 cetuximab, 1 both. Immediate progression with previous anti-EGFR was reported for 7 patients. Anti-BRAF was encorafenib for 21 patients, dabrafenib for 4 patients, with cetuximab for 24 patients and panitumumab for 1 patient. ORR was 40% (10 patients) and DCR was 80% (20 patients). Median PFS and OS were 4.8 months (95% CI, 4.01-7.95) and 10.1 months (95% CI, 7.75-NR). DCR amongst patients with previous primary resistance to anti-EGFR (N = 7) was 100%. Two patients discontinued B + E due to drug-related adverse event.

Conclusions: Though in a limited retrospective series of patients, these results show the efficacy of the combination of anti-BRAF and anti-EGFRs in BRAFm mCRC patients previously treated with an anti-EGFR. The use of this combination should thus not be ruled out in this population with limited therapeutic options.

Keywords: Anti-EGFRs; BRAF V600E mutation; BRAF inhibitors; Metastatic colon cancer.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carbamates* / therapeutic use
  • Cetuximab* / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Humans
  • Mutation
  • Panitumumab
  • Proto-Oncogene Proteins B-raf / genetics
  • Retrospective Studies
  • Sulfonamides* / therapeutic use


  • Carbamates
  • Sulfonamides
  • Panitumumab
  • encorafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Cetuximab