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

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).