"These data indicate that adjuvant therapy with pembrolizumab might become a treatment option for patients with resected stage IIB or IIC melanoma, but overall survival data are awaited," Dr. Jason J. Luke of the Hillman Cancer Center, University of Pittsburgh Medical Center, and colleagues conclude in The Lancet.
To the researchers' knowledge, theirs is the first phase-3 trial to show a significant reduction in the risk of recurrence or death with anti-PD-1 or anti-PD-L1 therapy in patients with completely resected, high-risk stage-II melanoma.
Recruited through 160 centers in 16 nations, patients were ages 12 and older with newly diagnosed, completely resected, histologically confirmed stage-IIB or -IIC cutaneous melanoma, without regional lymph node involvement.
The study team randomly assigned 976 patients (median age, 61; 60% male; 90% white) to receive intravenous pembrolizumab 200 mg or saline placebo every three weeks for 17 cycles.
The estimated 18-month recurrence-free survival rate was 86% with pembrolizumab and 77% with placebo, a significant difference. Distant metastases developed in the pembrolizumab arm at about half the rate of the placebo arm (6% vs. 12%).
The findings show pembrolizumab had "a manageable safety profile," the researchers say. They note that the results underpinned last year's U.S. approval of pembrolizumab as adjuvant treatment for adult and pediatric patients with high-risk stage-II and stage-III melanoma.
Dr. Luke told Reuters Health by email that the approval "functionally doubles the number of patients with melanoma who have pembrolizumab available as an adjuvant treatment after surgery."
Although anti-PD1 antibodies, such as pembrolizumab, have been approved for stage-III melanoma in the United States and elsewhere for years, he continued, "patients with stage IIB/C melanoma were not included in these clinical trials and therefore were not included under the regulatory approvals."
This was despite such patients having similar mortality risks after surgery as stage IIIA/B patients. This discrepancy, Dr. Luke explained, "was the impetus for the trial, which set out to essentially 'right a wrong' and make anti-PD1 immunotherapy available to patients with stage IIB/C disease."
"The use of adjuvant anti-PD1 antibodies for stage IIB/C and higher will further reduce the incidence of metastatic melanoma in the future," he predicted.
Dr. Julie R. Gralow, chief medical officer for the American Society of Clinical Oncology, told Reuters Health by email that the study showed pembrolizumab was associated with "a clear reduction in recurrences, most of them metastatic, which over time could lead to deaths."
She cautioned that because the authors "allowed cross-over at the time of recurrence (those who relapsed in either arm could get pembrolizumab), this may limit the ability to show a significant difference in mortality," given that pembrolizumab works well in the metastatic setting.
"The prior standard for stage-IIB/C melanoma was surgery alone, so this sets a new standard," Dr. Gralow concluded.
The trial was sponsored by Merck Sharp & Dohme, which makes pembrolizumab (Keytruda).
SOURCE: https://bit.ly/3O0iwWh The Lancet, online March 31, 2022.
By Scott Baltic
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