Adjuvant pembrolizumab shows benefit in patients with resected stage IIB, IIC melanoma
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CHICAGO — Adjuvant pembrolizumab significantly improved distant metastasis-free survival among patients with resected stage IIB or IIC melanoma, according to results of the phase 3 KEYNOTE-716 study presented at ASCO Annual Meeting.
Pembrolizumab (Keytruda, Merck), an anti-PD-1 antibody, also demonstrated a sustained recurrence-free survival benefit among these patients, with a positive benefit-risk profile.
“These results significantly increase the potential population of patients with melanoma who may benefit from treatment in the adjuvant setting,” Georgina V. Long, MD, PhD, FRACP, co-medical director of Melanoma Institute Australia and chair of melanoma medical oncology and translational research at the institute and Royal North Shore Hospital at The University of Sydney, told Healio.
Background and methods
The standard of care for patients with resected stage IIB and IIC melanoma has been observation, even though these patients have a risk for recurrence comparable to some patients with stage III disease, Long said.
“[These patients also] have similar 5-year survival outcomes as those with stage IIIB disease, for whom adjuvant treatment is standard of care,” she told Healio. “Five-year survival rates remain 87% for stage IIB and 82% for stage IIC, meaning approximately one in five patients at these earlier stages of the disease do not survive longer than 5 years.”
The KEYNOTE-716 trial sought to evaluate the efficacy of pembrolizumab — a standard of care as adjuvant therapy across substages of completely resected stage III melanoma — in stage IIB and IIC disease.
The trial enrolled 976 patients aged 12 years and older with resected stage IIB or IIC melanoma. Researchers randomly assigned study participants to either pembrolizumab, dosed at 200 mg for adults and 2 mg/kg (up to 200 mg) for pediatric patients every 3 weeks for about 1 year (n = 487), or placebo (n = 489).
The pembrolizumab and placebo groups had similar baseline characteristics, including median age (60 years vs. 61 years). About 40% of patients were aged 65 years or older, and 65% of patients in each group had stage IIB vs. IIC disease.
Treatment continued until disease recurrence or unacceptable toxicity.
RFS per investigator assessment served as the primary endpoint. Key secondary endpoints included distant metastasis-free survival (DMFS) and OS.
Long reported results at median follow-up of 27.4 months (range, 14-39.4).
Key findings
Results showed pembrolizumab significantly extended DMFS compared with placebo (median not reached in either group; HR=0.64; 95% CI, 0.47-0.88), with higher rates of DMFS at 12 months (94.7% vs. 90.2%) and 24 months (88.1% vs. 82.2%). The benefit spanned key subgroups, including T subcategory, age, sex, race, ECOG status and geographic region.
Researchers observed distant metastases as a first recurrence among fewer patients in the pembrolizumab vs. placebo group (n = 45 vs. 79) and mostly in the lungs (n = 31 vs. 69).
Patients in the pembrolizumab group also exhibited a sustained RFS benefit vs. those in the placebo group (HR = 0.64; 95% CI, 0.5-0.84), with RFS rates of 81.2% vs. 72.8% at 24 months. Distant vs. locoregional recurrences appeared more common in the placebo group (55% vs. 40%) than in the pembrolizumab group (47% vs. 48%).
Long reported no new safety signals in the pembrolizumab group.
Treatment-related adverse events occurred among 83% of patients in the pembrolizumab group (17% grade 3 or higher) compared with 64% of patients in the placebo group (5% grade 3 or higher). In addition, 16% of patients on pembrolizumab discontinued treatment vs. 2% on placebo, and 38% vs. 9% experienced immune-mediated events and infusion reactions.
The most common treatment-related events included fatigue (21% pembrolizumab vs. 19% placebo), pruritus (25% vs. 11%), diarrhea (19% vs. 12%), arthralgia (17% vs. 8%) and hypothyroidism (16% vs. 3%).
No patients died due to treatment-related adverse events.
Next steps
Disease assessment will continue every 6 months in years 2 to 4, then once in year 5, or as clinically indicated. The trial also will continue to evaluate for the secondary endpoint of OS, Long told Healio.
Collapse
Long GV, et al. Abstract LBA9500. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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