In the phase II ANCHOR CRC trial reported in the Journal of Clinical Oncology, Eric Van Cutsem, MD, PhD, and colleagues found that the combination of encorafenib, binimetinib, and cetuximab produced an objective response in nearly half of previously untreated patients with BRAF V600E–mutant metastatic colorectal cancer.
Eric Van Cutsem, MD, PhD
The study included 95 patients from sites in Austria, Belgium, France, Italy, Japan, the Netherlands, Spain, the United Kingdom, and the United States. They received encorafenib at 300 mg once daily and binimetinib at 45 mg twice daily in 28-day cycles, plus cetuximab at 400 mg/m2 on day 1 of cycle 1, then at 250 mg/m2 once weekly for the first seven cycles, and at 500 mg/m2 once on days 1 and 15 from cycle eight onward. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was locally assessed confirmed objective response rate. The null hypothesis of the true response rate being 30% was rejected if the lower limit of the 95% confidence interval (CI) for response rate was > 30%.
Objective responses (all partial responses) were observed in 45 patients (47.4%, 95% CI = 37.0%–57.9%), with the lower limit of the 95% confidence interval exceeding the prespecified rate of > 30%. Stable disease was observed in an additional 41.1% of patients, yielding a disease control rate of 88.4%. Median response duration was 5.1 months (95% CI = 3.8–8.5 months).
Median duration between first study treatment administration and data cutoff was 20.1 months.
Median progression-free survival was 5.8 months (95% CI = 4.6–6.6 months). Median overall survival was 18.3 months (95% CI = 14.1–21.1 months), with estimated 12-, 18-, and 24-month rates of 65%, 50%, and 35%, respectively. A total of 60% of patients received subsequent antineoplastic therapy after disease progression.
The most commonly reported grade ≥ 3 adverse events were anemia (11%), asymptomatic lipase increase (11%), diarrhea (10%), and nausea (8%). Serious adverse events occurred in 52% of patients, most commonly intestinal obstruction (17%) and renal failure (8%).
Adverse events led to discontinuation of at least one study drug in 24% of patients. Adverse events led to death in three patients, with causes consisting of intestinal obstruction (considered unrelated to treatment) and acute renal failure and pneumonitis (suspected to be treatment-related).
On the Patient Global Impression of Changes instrument, substantial improvement in symptoms (much or very much improved) was consistently reported in ≥ 30% of patients (range = 30%–52%) from cycle 3 to cycle 10.
The investigators concluded, “The ANCHOR CRC study showed that the scientifically driven combination of encorafenib, binimetinib, and cetuximab was active in the first-line setting of BRAF V600E–mutated metastatic colorectal cancer with a manageable safety profile. Further first-line evaluation is ongoing (ClinicalTrials.gov identifier NCT04607421).”
Eric Van Cutsem, MD, PhD, of University Hospitals Gasthuisberg/Leuven & KU Leuven, Leuven, Belgium, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pierre Fabre and a grant from the U.S. National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.