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BEACON Colorectal Cancer Trial: Safety Lead-in With Triplet Therapy for BRAF V600E–Mutant Metastatic Disease

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Key Points

  • Dose-limiting toxicities consisted of serous retinopathy in 2 patients, reversible decreased left-ventricular ejection fraction in 1 patient, and cetuximab-related infusion reactions in 2 patients.
  • The objective response rate was 48%.

As reported in the Journal of Clinical Oncology by Van Cutsem et al, treatment with encorafenib, binimetinib, and cetuximab for BRAF V600E–mutant metastatic colorectal cancer was associated with a manageable safety profile and evidence of activity in the safety lead-in to the phase III BEACON Colorectal Cancer trial.

Prior to the randomized portion of the trial, 30 patients with BRAF V600E–mutant metastatic colorectal cancer who had experienced treatment failure with 1 or 2 prior regimens participated in a safety lead-in phase. They received encorafenib at 300 mg daily, binimetinib at 45 mg twice daily, and cetuximab at 400 mg/m2 followed by 250 mg/m2 in 28-day cycles. The primary endpoint was safety, including the incidence of dose-limiting toxicities.

Safety Profile

Dose-limiting toxicities occurred in 5 patients, consisting of serous retinopathy in 2, reversible decreased left-ventricular ejection fraction in 1, and cetuximab-related infusion reactions in 2. The most common adverse events of any grade were diarrhea (77%), dermatitis acneiform (67%), fatigue (63%), and nausea (63%). The most common grade 3 or 4 adverse events were fatigue (13%), anemia (10%), increased creatine phosphokinase (10%), increased aspartate transaminase (10%), and urinary tract infection (10%). At least 1 drug was discontinued in 6 patients due to adverse events.

Responses

The median duration of follow-up was 18.2 months, and the median time on study drug was 7.9 months. Among 29 patients with BRAF V600E–mutant tumors (1 patient had a non–BRAF V600E–mutant tumor and was not included in the efficacy analysis), the confirmed overall response rate was 48%, median duration of response was 5.5 months, median progression-free survival was 8.0 months, and median overall survival was 15.3 months.

The investigators concluded, “In the safety lead-in, the safety and tolerability of the encorafenib, binimetinib, and cetuximab regimen is manageable and acceptable for initiation of the randomized portion of the study. The observed efficacy is promising compared with available therapies and, if confirmed in the randomized portion of the trial, could establish this regimen as a new standard of care for previously treated BRAF V600E–mutant metastatic colorectal cancer.”

Scott Kopetz, MD, PhD, of the Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study is sponsored by Array BioPharma. The study authors’ full disclosures can be found at ascopubs.jco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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