Jeffrey S. Weber
CHICAGO — Patients with surgically resected stage III or stage IV melanoma at high risk for recurrence maintained longer RFS after adjuvant treatment with nivolumab then standard ipilimumab, according to long-term efficacy results from the CheckMate 238 clinical trial presented at ASCO Annual Meeting.
“These more mature data continue to demonstrate durable clinical benefit with nivolumab and further support its use for resected stage III or IV melanoma,” Jeffrey S. Weber, MD, PhD, deputy director of Perlmutter Cancer Center at NYU Langone Health, said during his presentation.
CheckMate 238 is the first trial designed to compare nivolumab (Opdivo, Bristol-Myers Squibb), an anti-PD-1 antibody, and ipilimumab (Yervoy, Bristol-Myers Squibb), a CTLA-4 antibody, as adjuvant therapy for patients with resected stage III or stage IV melanoma at high risk for recurrence, defined as greater than 50% risk for relapse over 5 years.
Both agents are approved for treatment of advanced melanoma. Ipilimumab also is approved in the United States for treatment of resected stage III melanoma.
Earlier results of CheckMate 238 demonstrated prolonged RFS with nivolumab compared with standard ipilimumab in this patient population. For this analysis, Weber and colleagues reported on long-term efficacy results with an additional 6 months of follow-up.
The analysis included 906 patients aged 15 years or older. The majority (81%) of patients had stage III disease, 32% had ulcerated primary melanoma, 48% had macroscopic lymph node involvement and 42% harbored BRAF mutations.
Researchers randomly assigned patients to 3 mg/kg nivolumab via IV every 2 weeks (n = 453; median age, 56 years) or 10 mg/kg ipilimumab every 3 weeks for four doses, then every 12 weeks from week 24 up to 1 year (n = 453; median age, 54 years).
Treatment continued until disease recurrence or unacceptable toxicity. RFS in the intent-to-treat population served as the primary endpoint. Secondary endpoints included OS, safety and tolerability, RFS by PD-L1 tumor expression and health-related quality of life.
Minimum follow-up was 2 years.
A total 171 recurrent events occurred among patients who received nivolumab and 221 for patients who received ipilimumab. The RFS benefit with nivolumab compared with ipilimumab persisted with longer follow-up (30.8 months vs. 24.1 months; HR = 0.66; P < .0001).
The 2-year RFS rate was higher among patients who received nivolumab than ipilimumab in subgroups defined by disease stage (stage IIIB, 70.8% vs. 60.7%; stage IIIC, 58% vs. 45.4%; stage IV, 58% vs. 44.3%), PD-L1 expression ( 5%, 75.5% vs. 58.4%; < 5%, 55.2% vs. 45.5%) and BRAF mutation status (mutated, 61.9% vs. 51.7%; wild type, 63.5% vs. 46.2%).
Distant metastatic-free survival at 2 years also continued to be significantly longer with nivolumab than with ipilimumab (70.5% vs. 63.7%; HR = 0.76; P = .034).
Researchers administered subsequent therapies to 31.1% of patients who received nivolumab and 41.1% who received ipilimumab.
No deaths were reported among the nivolumab group compared with five in the ipilimumab group.
“The numbers are very small and is an interesting trend, but it will take an awful lot of follow-up to see enough deaths to be able to make any statistical assessment of whether there really is a difference in survival,” Weber said.
Per protocol, there was no additional safety assessment for the long-term analysis because patients stopped treatment more than 100 days prior to previous data cutoff. – by Melinda Stevens
Weber JS, et al. Abstract 9502. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Weber reports stock and other ownership interests in, consultant/advisory roles with, research funding to his institution from, or travel expenses from AbbVie, Altor BioScience, Amgen, Astellas Pharma, AstraZeneca, Biond, Bristol-Myers Squibb, cCam Biotherapeutics, Celldex, CytomX Therapeutics, Daiichi Sankyo, Eisai, Genentech, GlaxoSmithKline, Ichor Medical Systems, Incyte, Lion Biotechnologies, Medivation, Merck, Nektar, Novartis, Pieris Pharmaceuticals, Roche, Sellas Life Sciences and WindMIL. He also is named on a patent from Biodesix for a PD-1 antibody biomarker, and on a patent submitted by Moffitt Cancer Center for an ipilimumab (Yervoy, Bristol-Myers Squibb) biomarker. Please see the abstract for all other authors’ relevant financial disclosures.