Scott Kopetz, MD @skopetz of @MDAndersonNews discusses what’s next for the phase 3 BEACON trial in colorectal cancer.
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Pfizer Inc. (NYSE: PFE) today announced detailed results from the interim analysis of the Phase 3 BEACON CRC trial evaluating the combination of BRAFTOVI® (encorafenib), MEKTOVI® (binimetinib), and cetuximab (BRAFTOVI Triplet), in patients with advanced BRAFV600E-mutant metastatic colorectal cancer (mCRC), following one or two lines of therapy. The results show significant improvements in overall survival (OS) and objective response rates (ORR) for the BRAFTOVI Triplet and BRAFTOVI Doublet combination (BRAFTOVI and cetuximab), compared to cetuximab plus irinotecan-containing regimens (Control), and provide analysis of the efficacy and safety of the BRAFTOVI Triplet compared to the BRAFTOVI Doublet. These data will be presented today during a late-breaking oral session at the 2019 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain, and simultaneously published online in The New England Journal of Medicine (NEJM). Pfizer intends to submit the results of the BEACON CRC trial for marketing approval in the U.S. in the fourth quarter of 2019. The use of BRAFTOVI, MEKTOVI and cetuximab for the treatment of patients with BRAFV600E-mutant mCRC is investigational and not approved by the FDA.
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As previously announced, the BRAFTOVI Triplet showed a median OS of 9.0 months for patients treated with the Triplet, compared to 5.4 months for Control ([HR 0.52, (95% CI 0.39-0.70), p<0.0001]). The BRAFTOVI Triplet also demonstrated a significantly improved ORR of 26% (95% CI: 18%, 35%) compared to 2% (95% CI: 0%, 7%) for Control (p<0.0001).
“We are pleased to share these data from the BEACON CRC trial with the oncology community,†said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “With no approved therapies currently indicated specifically for BRAF-mutant mCRC, we believe that the evidence so far shows encouraging potential for the BRAFTOVI Triplet to make a meaningful impact on the lives of those living with this disease.â€
The study also showed improvements in secondary efficacy endpoints. As previously announced, the BRAFTOVI Doublet showed a statistically significant improvement in OS (median 8.4 months vs. 5.4 months, [HR 0.60, 95% CI (0.45-0.79), p=0.0003]) compared to Control. Additional analysis showed depth of responses in favor of the BRAFTOVI Triplet.
“The BEACON CRC trial results show meaningful improvements compared to an available standard of care for patients with BRAFV600E-mutant mCRC,” said Scott Kopetz, M.D., Ph.D., FACP, Associate Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “These data presented at ESMO and published in The NEJM further support the potential of the BRAFTOVI Triplet to be the first chemotherapy-free, targeted regimen for this patient population, who have a poor prognosis and limited treatment options.”
Further, the data provide additional details on the primary and secondary endpoints, including observations of response rates by number of lines of prior therapy, as well as a descriptive analysis of OS comparing the BRAFTOVI Triplet to the BRAFTOVI Doublet.
The BEACON CRC study was not powered to compare the two experimental arms directly and such a comparison is further limited by the interim nature of the analysis. In the data being presented at ESMO, results of the descriptive analysis of survival comparing the BRAFTOVI Triplet to the BRAFTOVI Doublet favored the Triplet combination.
As previously reported, the BRAFTOVI Triplet and Doublet were generally well-tolerated with no unexpected toxicities. Grade 3 or higher adverse events (AEs) were seen in 58%, 50% and 61% of patients in the BRAFTOVI Triplet, Doublet and Control arms, respectively. Discontinuation of therapy due to adverse events was seen in 7%, 8% and 11% of patients in the Triplet, Doublet and Control arms, respectively. The most common Grade 3 or higher AEs seen in patients treated with the BRAFTOVI Triplet were diarrhea (10% vs. 2% in the Doublet arm and 10% in the Control arm), abdominal pain (6% vs. 2% in the Doublet arm and 5% in the Control arm) and nausea (5% vs. <1% in the Double arm and 1% in the Control arm).