According to the National Cancer Institute’s SEER data, the five-year survival rate for metastatic melanoma among patients diagnosed between 2009 and 2015 was 24.8 percent.
Early results from the BRIM7 phase I clinical trial evaluating the BRAF V600E inhibitor vemurafenib in combination with the MEK1 inhibitor cobimetinib in patients with BRAF V600E metastatic melanoma have been previously reported.
They showed that 87 percent of patients who received the combination and had not previously been treated with a BRAF-targeted therapeutic had a partial or complete response.
This study provides extended follow-up results from the trial, including overall survival (OS) data.
“When this study was initiated, the treatments available yielded long-term benefit at four or five years for only about 10 percent of patients diagnosed with metastatic melanoma,” said Ribas. “The fact that a subgroup of patients were alive and well at the five-year follow-up mark after this combination treatment is remarkable.”
These findings have been published in the journal Clinical Cancer Research.
The researchers enrolled two cohorts of patients with advanced BRAF V600E-mutant melanoma.
The first cohort, which had 63 patients, had not previously been treated with a BRAF-targeted therapeutic and were referred to as BRAF inhibitor-naïve; the second cohort, which had 66 patients, had progressed on prior treatment with vemurafenib monotherapy.
The data cutoff for this follow-up study was May 25, 2018.
At the time of the extended follow-up, the median OS in the BRAF inhibitor-naïve cohort was 31.8 months; the OS rate plateaued at roughly four years of follow-up at 39.2 percent.
The median OS for patients who had progressed on prior vemurafenib monotherapy was 8.5 months; the OS rate plateaued at 14 percent at roughly three years of follow-up.
Treatment-related adverse events were similar to those previously reported with this drug combination.
However, both cohorts had increases in photosensitivity reactions and actinic keratitis due to longer-term exposure.
“A subset of patients derived long-term benefit from this therapeutic strategy, indicating that targeted therapies are a viable option for patients with BRAF-mutant melanoma,” Ribas said. “With the goal of increasing the number of patients with long-term benefit, clinical trials investigating dual BRAF and MEK inhibition in combination with PD-1 or PD-L1 blocking antibodies are currently underway.”
"Some patients may have received PD-1 blockade treatments after experiencing progression during this clinical trial and may have derived long-term benefit from such immunotherapy treatments, representing a limitation of this study," Ribas noted.