ASCO: BRAF Inhibitor Cuts Death Risk in Advanced Melanoma
FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Survival estimates at a median 3 months' of follow-up suggest 84% of patients treated with vemurafenib would be alive at 6 months vs. 64% of those in a control group treated with dacarbazine.
Data Source: The randomized, open-label, phase III BRIM-3 trial in 675 patients with newly diagnosed stage III or IV melanoma.
Disclosures: Genentech sponsored the BRIM-2 and BRIM-3 trials. Dr. Chapman reported consultant/advisory roles and research funding from its parent company Roche. Some coauthors were Roche employees, and others reported similar relationships with Genentech. Dr. Ribas and several of his co-authors reported similar consulting and advisory relationships with Roche/Genentech. Dr. Schuchter had no disclosures. Dr. Ernstoff made no relevant financial conflicts of interest.
CHICAGO — A closely watched experimental drug has come through with a 63% reduction in the relative risk of death from metastatic melanoma when compared with standard therapy in a phase III trial that had enrolled 675 newly diagnosed patients.
Vemurafenib (better known as PLX4032) targets the BRAF V600E mutation found in 40%-60% of melanoma patients. It is only the second melanoma drug to extend the lives of melanoma patients in a randomized clinical study.
The first such agent, ipilimumab (Yervoy), was approved earlier this year, and the melanoma community expects the Food and Drug Administration will award an indication to vemurafenib based on the new data from the BRIM-3 trial.
The prospect of two new drugs for advanced melanoma is "really unprecedented," said Dr. Lynn Schuchter, moderator of a press briefing at the American Society of Clinical Oncology annual meeting, where BRIM-3 results were presented in a plenary session. They were published simultaneously in the New England Journal of Medicine (10.1956NEJMOa1103782).
The BRIM-3 study and ipilimumab data also presented at the meeting will provide the foundation for further research into how to optimize therapy for the disease, said Dr. Schuchter, division chief of hematology-oncology at the Abramson Cancer Center at the University of Pennsylvania in Pittsburgh.
Indeed, just how to incorporate both drugs into clinical practice was a hot topic at the meeting, as up to now oncologists have had few therapeutic options to offer patients with advanced melanoma.
"It’s wonderful to have this problem. The melanoma community is still trying to sort this out," said Dr. Paul Chapman, lead author of the BRIM-3 study and an attending-physician at Memorial Sloan-Kettering Cancer Center in New York. The drug companies developing both drugs– Bristol-Myers Squibb behind ipilimumab and Genentech behind vemurafenib – are already planning a study of them in combination, he added.
Among the dramatic early results from BRIM-3, Dr. Chapman reported estimates that 84% of patients treated with oral vemurafenib but only 64% of those given dacarbazine (DTIC) would be alive at 6 months. The hazard ratio for death was 0.37 (P less than .0001), and an analysis of progression-free survival showed a 74% reduction in the risk of progression (HR 0.26, P less than .0001). Median time to progression was 5.3 months with vemurafenib vs. 1.6 months with dacarbazine, he said.
A Major Defining Moment
"For patients with metastatic melanoma with the BRAF V600E mutation, the availability of vemurafenib is a major defining moment that will have an important impact on survival and quality of life. Vemurafenib will be part of our therapeutic armamentarium for patients with melanoma and potentially for those with other cancers harboring BRAF V600E mutations, as well as a valuable tool for exploring new approaches to melanoma treatment."
Dr. Marc S. Ernstoff of the Dartmouth–Hitchcock Medical Center, Lebanon, N.H., made these comments in an accompanying editorial and reported no relevant financial conflicts (10.1956NEJMe11057792). </i>