We already know that vemurafenib significantly improves response rates, progression-free survival, and six-month survival in advanced melanoma patients with BRAF-mutant tumors. So the news that the drug improves overall survival is not a surprise. But it is good to see the data, published in today’s New England Journal of Medicine.
Median overall survival for 132 patients enrolled in the phase II trial (BRIM2) was 15.9 months, according to the new analysis.
Because this was a single-arm phase II trial, we have no direct benchmark for comparison. However, senior author
Antoni Ribas, MD, PhD, Professor of Hematology/Oncology and a researcher at the Jonsson Cancer Center at the University of California, Los Angeles, estimates that the expected survival for these patients with any other agent would be between six and nine months.
By that measure – which come with a grain of salt – vemurafenib more than doubles overall survival.
Despite the problems associated with cross-trial comparison or comparing trial outcomes with historical survival, the phase II single-arm data are going to be the best survival data we will get for vemurafenib.
Dr. Ribas noted in an email to me that because the phase III trial (BRIM3) was stopped so early -- just one month after the last patient was enrolled -- follow-up has been relatively short. And patients in the chemotherapy arm were allowed to cross over to vemurafenib at that early time point.
Therefore, even with longer follow-up, the phase III overall survival data will be seriously compromised, if not completely useless.
So, imperfect as single-arm data are, they are the data we have. The good news is that with such a large improvement in survival, we don’t need to worry that it is just an artifact of the out-of-trial comparison. The drug really does improve survival; we might not know the exact magnitude of the benefit, but the benefit is clearly and dramatically there.