This is a relatively small phase II study, but the data are very provocative and show significant efficacy. I think many oncologists are going to be much in favor of using this regimen in these patients.— Frank A. Sinicrope, MD
Frank A. Sinicrope, MD, Professor of Medicine and Oncology at the Mayo Clinic, Rochester, Minnesota, told The ASCO Post that the regimen of irinotecan/cetuximab (Erbitux)/vemurafenib (Zelboraf) could be an important approach to treating this challenging tumor subtype.
“BRAF-mutated tumors have a poor prognosis, and more effective therapy in this subtype is a major unmet need. Preclinical data have suggested that we need to inhibit both BRAF and EGFR simultaneously, because of the feedback EGFR activation that occurs when you block BRAF,” he said. “This study demonstrates that what we see experimentally is indeed true for patients—that when we combine BRAF and EGFR inhibitors, we achieve higher response rates and improved outcomes compared to EGFR inhibition alone.”
The study is also a laudable example of an effective biomarker-driven clinical trial in a rare tumor subtype, he added.
Dr. Sinicrope commented on the co-occurrence of microsatellite instability (MSI)-high status and BRAF mutation. “Sporadic MSI-H tumors frequently have BRAF mutations, and while we generally think of [patients with] MSI-H tumors as having better outcomes, our data and those of Dr. Kopetz suggest that when tumors recur or metastasize, BRAF confers tumor aggressiveness, and MSI-high status does not seem to provide much protection.”
Analysis of MSI status in the study cohort is planned, and since BRAF mutation is associated with a higher rate of peritoneal metastasis, with such tumors having among the worst outcomes, it will be important to determine whether these patients were balanced between the study arms.
“This is a relatively small phase II study, but the data are very provocative and show significant efficacy,” concluded Dr. Sinicrope. “Based on these data, I think many oncologists are going to be much in favor of using this regimen in these patients.” ■
Disclosure: Dr. Sinicrope reported no potential conflicts of interest.
In patients with metastatic colorectal cancer who have mutations in BRAF V600, the addition of the BRAF inhibitor vemurafenib (Zelboraf) to cetuximab (Erbitux) and irinotecan significantly improved progression-free survival, results of the phase II Southwest Oncology Group (SWOG) 1406 trial have...