Atezolizumab combination extends PFS in BRAF V600-mutant advanced melanoma
The addition of atezolizumab to cobimetinib and vemurafenib significantly prolonged PFS and conferred durable responses among patients with BRAF V600 mutation-positive advanced melanoma, according to results of the randomized phase 3 IMspire150 study presented at the virtual American Association for Cancer Research Annual Meeting.
The treatment also appeared tolerable, researchers noted.
“Overall, the addition of atezolizumab led to a clinically meaningful benefit compared with cobimetinib and vemurafenib alone,” Grant A. McArthur, MBBS, PhD, FRACP, executive director of Victorian Comprehensive Cancer Centre, head of the molecular oncology laboratory and senior consultant medical oncologist at Peter MacCallum Cancer Centre in Australia, said during the presentation. “The safety profile was consistent with the known risks for each individual drug. There were no new safety signals observed.”
Current systemic treatments for advanced melanoma include immune checkpoint inhibitors and targeted therapy with BRAF and MEK inhibitors for BRAF V600E- or V600K-mutant melanoma. Response rates generally are lower with checkpoint inhibitors than with targeted therapy, but responses tend to be more durable.
Previous studies have suggested that checkpoint inhibitors and BRAF plus MEK inhibitors could work well together.
“Collectively, these data led to the hypothesis that combining checkpoint inhibitors with BRAF and MEK inhibitors may overcome the clinical limitations of individual classes of therapy and potentially lead to more durable responses,” McArthur said.
The study included 514 treatment-naive patients with unresectable stage IIIc or stage IV melanoma and BRAF V600 mutations.
McArthur and colleagues randomly assigned 256 patients to a combination of the anti-PD-L1 antibody atezolizumab (Tecentriq, Genentech/Roche), the MEK inhibitor cobimetinib (Cotellic, Genentech) and the BRAF inhibitor vemurafenib (Zelboraf, Genentech). The other 258 patients received placebo plus cobimetinib and vemurafenib.
Treatment continued until disease progression or unacceptable toxicity. PFS served as the primary endpoint.
Median follow-up was 18.9 months.
Results showed superior PFS in the atezolizumab group (15.1 months vs. 10.6 months; HR = 0.78; 95% CI, 0.63-0.97).
Researchers observed similar objective response rates in both groups; however, median duration of response was longer with atezolizumab than placebo (21 months vs. 12.6 months).
Common treatment-related adverse events in the atezolizumab combination and placebo combination groups included blood creatinine phosphokinase increase (51.3% vs. 44.8%), diarrhea (42.2% vs. 46.6%), rash (40.9% in both), arthralgia (39.1% vs. 28.1%), pyrexia (38.7% vs. 26%), alanine aminotransferase increase (33.9% vs. 22.8%) and lipase increase (32.2% vs. 27.4%).
Common grade 3 and grade 4 adverse events in both groups included lipase increase (20.4% vs. 20.6%), blood creatinine phosphokinase increase (20% vs. 14.9%), alanine aminotransferase increase (13% vs. 8.9%) and maculopapular rash (12.6% vs. 9.6%). Both groups had similar incidence of serious treatment-related adverse events (33.5% vs 28.8%).
About 12.6% of patients in the atezolizumab group and 15.7% of patients in the placebo group stopped treatment because of adverse events.
“The OS data are not yet mature, but it does favor the atezolizumab group so far,” McArthur said. “That will be something that will be followed up with.”– by John DeRosier
McArthur GA, et al. Abstract CT012. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).
Disclosures: McArthur reports reimbursement of costs for clinical trials to his institution from Array BioPharma and Genentech/Roche. Please see the abstract for all other researchers’ relevant financial disclosures.