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

Taieb, J; Lonardi, S; Desai, J; Folprecht, G; Gallois, C; Marques, EP; Khan, S; Castagne, C; Wasan, H

Author(s): Taieb, J; Lonardi, S; Desai, J; Folprecht, G; Gallois, C; Marques, EP; Khan, S; Castagne, C; Wasan, H;
Details: Publication Year 2023-03,Volume 22,Issue #1,Page 59-66
Journal Title: Clinical Colorectal Cancer
Publication Type: Research article
Abstract: BACKGROUND: The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with BRAF(V600E)-mutated (BRAF(V600E)mut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in BRAF(V600E)mut 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).
Publisher: Elsevier
Keywords: Male; Humans; Female; Cetuximab; *Colorectal Neoplasms/drug therapy/genetics; Asthenia/chemically induced; Proto-Oncogene Proteins B-raf/genetics; Myalgia/chemically induced/drug therapy; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *Colonic Neoplasms/drug therapy; *Rectal Neoplasms/drug therapy; Vomiting/chemically induced; Nausea/chemically induced; Fatigue/etiology; Mutation; BRAF inhibitors; Biomarkers; Toxicity; enco+cetux; mCRC
Department(s): Medical Oncology
PubMed ID: 36653241
Publisher's Version: https://doi.org/10.1016/j.clcc.2022.12.003
Open Access at Publisher's Site: https://doi.org/10.1016/j.clcc.2022.12.003
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-07-11 06:23:37

Last Modified: 2023-07-11 06:25:37