Support for adjuvant pembrolizumab in earlier-stage melanoma
NEW YORK 22/09 - Treatment with pembrolizumab reduced cancer recurrence after surgery in patients with stage-IIb and -IIc melanoma in the phase-3 KEYNOTE-716 trial.
Pembrolizumab is anti-PD-1 immunotherapy currently approved only for stage-III and -IV melanoma. The KEYNOTE-716 study evaluated the benefit of pembrolizumab in earlier-stage melanoma.
"One misnomer in the field of melanoma is that earlier stage - meaning stage-II melanoma - might be lower-risk than stage III. But in fact, melanoma-specific survival of stage IIb and IIc melanoma is similar to stage IIIa and IIIb," Dr. Jason Luke of the University of Pittsburgh and UPMC Hillman Cancer Center said in reporting the results at the European Society for Medical Oncology (ESMO) 2021 Congress.
KEYNOTE-716 enrolled 976 patients with stage-IIb or -IIc melanomas. Following surgery, 487 patients received intravenous pembrolizumab and 489 received a placebo every three weeks for one year. Patients were monitored for cancer recurrence via CT scans and magnetic-resonance imaging.
At a median follow-up 14.4 months, 136 patients had disease recurrence or died: 54 in the pembrolizumab group and 82 in the placebo group.
"What we observed was a substantial improvement in recurrence-free survival, such that the trial met its prespecified primary endpoint of recurrence-free survival at the first assessment, with a hazard ratio of 0.65 or a 35% reduction in the risk of recurrence," Dr. Luke reported.
Patient monitoring for cancer recurrence or death is ongoing. "The trial is still very early, and we expect to see the benefit of pembrolizumab increase above 35% over time," Dr. Luke said in a news release.
Pembrolizumab was associated with the known toxicity spectrum of the drug. The incidence of grade-3 or -4 adverse events was 16.1% with pembrolizumab versus 4.3% with placebo; 15.3% of patients discontinued pembrolizumab due to a drug-related adverse event versus 2.5% of placebo patients.
Immune-mediated adverse events were reported in 36.2% of patients on pembrolizumab versus 8.4% of patients on placebo.
"Pembrolizumab is used for many different diseases and we saw nothing new that would make us concerned about the use of it in this population. Quality of life was similar between the placebo and pembrolizumab groups at all time points," Dr. Luke said.
In a press release, Merck, which makes pembrolizumab and funded the study, said the findings have been accepted for priority review by the U.S. Food and Drug Administration for use of pembrolizumab in stage-IIb and -IIc melanoma (https://bit.ly/3tZs5Lp).
"The stage-IIb and -IIc population is approximately the same size as the entirety of stage-III melanoma. So in fact, these results should lead to a doubling of the population who have may have access to pembrolizumab as adjuvant therapy for melanoma," Dr. Luke said.
ESMO-invited discussant for the trial, Dr. Omid Hamid of The Angeles Clinic and Research Institute, a Cedars-Sinai affiliate, in Los Angeles, called the data "amazing" and noted that this is "the first phase-3, randomized, double-blind study of anti PD-1 therapy for patients with resected, stage-IIb and -IIc melanoma."
The results have "really sabotaged how we think about how we treat our patients and how we're going to think about what we do in the future as we leave ESMO," Dr. Hamid said.
Dr. Hamid cautioned, however, that the "current problem is that we don't know who benefits (from adjuvant therapy) and there is a subset of patients that never recur without therapy." He emphasized the need for "predictive biomarkers in order to exclude some patients from toxicity."
Dr. Luke has disclosed relationships with Merck and other pharmaceutical companies.
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