Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study

Clin Colorectal Cancer. 2023 Mar;22(1):59-66. doi: 10.1016/j.clcc.2022.12.003. Epub 2022 Dec 24.

Abstract

Background: The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with BRAFV600E-mutated (BRAFV600Emut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in BRAFV600Emut mCRC patients who had progressed after 1-2 previous regimens. This analysis provides a detailed examination of the adverse events (AEs) of interest (AEIs) with encorafenib+cetuximab in the BEACON study to aid gastrointestinal oncologists, given the limited experience with this combination.

Materials and methods: AEIs, including dermatological AEs, arthralgia/myalgia, nausea/vomiting, diarrhea, abdominal pain, fatigue/asthenia and nephrotoxicity, were examined in the doublet therapy group. Clinical characteristics associated with these AEs, AE grade, time to onset and time to resolution were also studied.

Results: Safety analysis included 216/220 patients randomized to doublet therapy. The most commonly occurring AEI was dermatological toxicity (75.5%), followed by arthralgia/myalgia (56.0%) and fatigue/asthenia (56.0%). Other than nephrotoxicity (7 patients; 5/7 with Grade 3 or 4), most AEs were Grade 1 or 2. Most AEs were more common in women than men (nausea/vomiting, diarrhea, abdominal pain, dermatological AEs, and arthralgia/myalgia). Nausea/vomiting, abdominal pain and fatigue/asthenia were more common in patients aged ≥70 years. Most AEs developed early, within the first 1-2 months of treatment, and resolved within 1-2 weeks. In addition, survival outcomes were better in patients experiencing arthralgia/myalgia or dermatological toxicities.

Conclusion: This analysis indicated that, except for rare cases of nephrotoxicity, encorafenib+cetuximab is well tolerated in most patients, with most AEIs being mild-to-moderate in severity, occurring early and resolving rapidly.

Clinical trial registration: the BEACON study (ClinicalTrials.gov, NCT02928224; EudraCT, 2015-005805-35).

Keywords: BRAF inhibitors; Biomarkers; Toxicity; enco+cetux; mCRC.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asthenia / chemically induced
  • Cetuximab
  • Colonic Neoplasms* / drug therapy
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Fatigue / etiology
  • Female
  • Humans
  • Male
  • Mutation
  • Myalgia / chemically induced
  • Myalgia / drug therapy
  • Nausea / chemically induced
  • Proto-Oncogene Proteins B-raf / genetics
  • Rectal Neoplasms* / drug therapy
  • Vomiting / chemically induced

Substances

  • encorafenib
  • Cetuximab
  • Proto-Oncogene Proteins B-raf

Associated data

  • ClinicalTrials.gov/NCT02928224