Updated results were recently reported from the 30 patient safety lead-in of the phase III BEACON CRC trial evaluating the triplet combination of encorafenib (a BRAF inhibitor), binimetinib (an MEK inhibitor), and cetuximab (Erbitux, an anti–EGFR antibody) in patients with BRAF-mutant metastatic colorectal cancer whose disease has progressed after one or two prior regimens. The data were presented by Van Cutsem et al at the 2018 Gastrointestinal (GI) Cancers Symposium (Abstract 627).
In patients with a BRAF V600E mutation, the estimated median progression-free survival at the time of analysis was 8 months. The confirmed overall response rate in patients with a BRAF V600E mutation was 48%, and three patients achieved complete responses. Further, the overall response rate was 62% in the 16 patients (10/16) who received only 1 prior line of therapy. These data represent substantial improvements compared to several separate historical published standard-of-care benchmarks for this population.
“We are very excited about these safety lead-in results, which show both an unprecedented progression-free survival and overall response rate in patients with BRAF V600–mutant colorectal cancer,” said Scott Kopetz, MD, PhD, FACP, Associate Professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “To put these data in context, the observed median progression-free survival of 8 months exceeds historical benchmarks of approximately 2 months for median progression-free survival, and 4 to 6 months for median overall survival, with current standards of care in this patient population. These results demonstrate the potential of the triplet combination to benefit this population of patients who currently have very limited effective treatment options.”
Safety and Adverse Events
In the safety lead-in, the triplet combination was generally well-tolerated. Two patients discontinued treatment due to adverse events, with only one of these considered related to treatment. The most common grade 3 or 4 adverse events seen in at least 10% of patients were fatigue (4/30), urinary tract infection (3/30), increased aspartate aminotransferase (3/30), and increased blood creatine kinase (3/30).
All patients with elevated baseline levels of the tumor markers CEA and CA19-9 had a reduction from baseline, with similar and substantial reductions (median = 83%–96%) across both markers in patients with objective responses and those with stable disease.
The enrollment in the randomized portion of the BEACON CRC trial is ongoing. Patients interested in participating in this trial may talk to their doctor to have their tumor tested for the BRAF mutation for eligibility to enroll in this new and important trial. Further details on the trial are available at clinicaltrials.gov (NCT02928224).
More About BEACON CRC
BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of encorafenib, binimetinib, and cetuximab in patients with BRAF-mutant metastatic colorectal cancer whose disease has progressed after one or two prior regimens. Thirty patients were treated in the safety lead-in and received the triplet combination (encorafenib at 300 mg daily, binimetinib at 45 mg twice daily, and cetuximab per label). Of the 30 patients, 29 had a BRAF V600E mutation. Microsatellite instability–high status, resulting from defective DNA mismatch repair, was detected in only 1 patient. As previously announced, the triplet combination demonstrated good tolerability, supporting initiation of the randomized portion of the trial.
The randomized portion of the BEACON CRC trial is designed to assess the efficacy of encorafenib in combination with cetuximab with or without binimetinib compared to cetuximab and irinotecan-based therapy. Approximately 615 patients are expected to be randomized 1:1:1 to receive triplet combination, doublet combination (encorafenib and cetuximab), or the control arm (irinotecan-based therapy and cetuximab).
The primary endpoint of the trial is overall survival associated with the triplet combination compared to the control arm. Secondary endpoints address the efficacy of the doublet combination compared to the control arm and the triplet combination compared to the doublet therapy. Other secondary endpoints include progression-free survival, overall response rate, duration of response, safety, and tolerability. Health-related quality-of-life data will also be assessed.
The trial will be conducted at over 250 investigational sites in North America, South America, Europe, and the Asia Pacific region. Patient enrollment is expected to be completed in 2018.
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