In a nutshell
This study examined the effectiveness of treatment with vemurafenib (Zelboraf) and cobimetinib (Cotellic) in metastatic (spread to other parts of the body) melanoma. Researchers suggested that this combination improves treatment outcomes.
PD-L1 is a protein present in the immune system that helps attacking cancer cells. Approximately 50% of melanoma patients have a mutation (permanent change) in the BRAF gene. The standard treatment for these patients is BRAF inhibitors such as vemurafenib. Although most patients have positive responses to these treatments, some patients do not have such a positive outcome. This can be due to drug resistance. This resistance happens due to the reactivation of the MAPK (a protein) pathway (which allows tumor growth). Therefore, adding a MAPK inhibitor (such as cobimetinib) helps overcome BRAF resistance.
Prior studies suggested that increased PD-L1 presence in the immune system cells is associated with better outcomes. However, the effectiveness of this combined treatment in patients with different amounts of PD-L1 cells is not clear.
Methods & findings
The objective of this study was to examine the effectiveness, including overall survival (OS; time from treatment to death by any cause) and progression-free survival (PFS; time from treatment to disease progression), in patients with different levels of PD-L1.
210 patients were enrolled and randomly assigned to receive either vemurafenib and cobimetinib (group 1) in combination or vemurafenib alone (group 2). Of these patients, 59.6% had low PD-L1 and 14.8% had high PD-L1 on their tumors.
The average follow-up time was 18.5 months. The average PFS in group 1 was 12.6 months and 7.2 months in group 2. The average OS in group 1 was 22.5 months and 17.4 in group 2.
Patients from group 2 with increased amounts of PD-L1 had a 30% improvement in the odds of a better PFS compared to patients with less PD-L1. These patients also had a 31% improvement in the odds of a better OS.
Patients from group 1 had similar PFS and OS regardless of PD-L1 levels.
The bottom line
This study suggested that vemurafenib/cobimetinib combined treatment may overcome the poorer prognosis associated with low levels of PD-L1.
The fine print
This study was funded by F Hoffmann-La Roche-Genentech, the producer of cobimetinib.
Published By :
Pigment Cell & melanoma Research
Nov 20, 2017