Big News for BRAF-Mutant Melanoma Patients
An international trial was conducted that studied patients with previously untreated advanced BRAF-mutant melanoma to the doublet or triplet regimens. Here is an overview of the results.
Triplet Succeeds in BRAF-Mutant Melanoma
Source: medpagetoday.com
Adding the PD-L1-directed immunotherapy atezolizumab (Tecentriq) to a targeted combination improved progression-free survival (PFS) for advanced melanoma patients with a BRAF V600 mutation, a phase III trial showed.
In over 500 patients receiving the BRAF/MEK inhibitor combination of vemurafenib (Zelboraf) plus cobimetinib (Cotellic) as initial therapy, those randomized to atezolizumab achieved a median investigator-assessed PFS of 15.1 months, as compared with 10.6 months for those assigned to placebo (HR 0.78, 95% CI 0.63-0.97, P=0.025), reported Grant McArthur, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia.email article
Adding the PD-L1-directed immunotherapy atezolizumab (Tecentriq) to a targeted combination improved progression-free survival (PFS) for advanced melanoma patients with a BRAF V600 mutation, a phase III trial showed.
In over 500 patients receiving the BRAF/MEK inhibitor combination of vemurafenib (Zelboraf) plus cobimetinib (Cotellic) as initial therapy, those randomized to atezolizumab achieved a median investigator-assessed PFS of 15.1 months, as compared with 10.6 months for those assigned to placebo (HR 0.78, 95% CI 0.63-0.97, P=0.025), reported Grant McArthur, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia.
Findings from IMspire150, presented at the American Association for Cancer Research (AACR) virtual meeting, showed superior investigator-assessed PFS favoring the triplet over the doublet at both 12 months (54.0% vs 45.1%) and 18 months (43.6% vs 31.6%).
“Patients with advanced BRAF-mutant melanoma can be treated with combinations of BRAF and MEK inhibitors that offer the advantage of high response rates — however, for many patients these responses are short-lived,” McArthur said. “Immune checkpoint inhibitors, in contrast, provide more durable responses, but have a lower response rate.”
While response rates in the trial were similar between the two arms (66.3% with the triplet and 65.0% with the doublet), the median duration of response was 21.0 months with atezolizumab and 12.6 months with placebo — a “clinically meaningful improvement,” said McArthur. At 1 year, 69.4% versus 50.8%, respectively, had maintained their responses.
An interim overall survival analysis favored the atezolizumab arm numerically (28.8 vs 25.1 months), and at 2 years, 60.4% of patients assigned to atezolizumab were alive versus 53.1% of those on placebo.
However, PFS as assessed by an independent review committee — a key secondary endpoint — failed to show statistical significance (median 16.1 months with the triplet vs 12.3 months with the doublet). Landmark analyses favored the atezolizumab arm at all time points analyzed:
- 6 months: 77.6% vs 75.3%
- 12 months: 54.8% vs 51.1%
- 18 months: 45.2% vs 36.9%
AACR invited discussant Charles Sawyer, MD, of Memorial Sloan Kettering Cancer Center in New York City, questioned whether the BRAF/MEK inhibitor control arm in IMspire150 was still relevant.
“Since the time this trial was initiated, the standard of care for these patients has changed and that’s based upon the remarkable benefit of giving combined checkpoint blockade,” he said, pointing to long-term results of CheckMate 067, which demonstrated a 5-year PFS rate of 38% for advanced melanoma patients with BRAF mutations treated upfront with the PD-1-directed agent nivolumab (Opdivo) plus ipilimumab (Yervoy), a CTLA-4-directed checkpoint inhibitor.
Unclear from the IMspire150 data, said Sawyer, is whether the targeted agents are indeed priming the tumor microenvironment for immunotherapy, thereby improving outcomes. He suggested the possibility that no synergy exists between the agents, and that patient-to-patient variability could simply be playing a role.
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