Pembrolizumab improved relapse-free survival (RFS) but not overall survival (OS), when compared with high-dose recombinant interferon alfa-2b (HDI) or high-dose ipilimumab, as adjuvant treatment in patients with high-risk resected melanoma enrolled in the intergroup S1404 trial.

These results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Kenneth F. Grossmann, MD, PhD, of Huntsman Cancer Center at the University of Utah in Salt Lake City.

The phase 3 trial (ClinicalTrials.gov Identifier: NCT02506153) was designed to test whether adjuvant pembrolizumab given over 1 year would improve survival compared with the two adjuvant treatments (ipilimumab and HDI) that were already approved to treat high-risk resected melanoma.


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The trial included adults with completely resected stage IIIA-IVC melanoma. Patients with uveal melanoma, brain metastases, autoimmune disease, a history of hepatitis B or C, and those treated with prior immunotherapy were excluded.

Patients were randomly assigned 1:1 to the control arm or the experimental arm. In the control arm, patients could choose to receive HDI (n = 146) or high-dose ipilimumab (n = 465). In the experimental arm (n = 648), patients received pembrolizumab at 200 mg IV every 3 weeks for 52 weeks.

There were no significant differences in baseline patient and tumor characteristics between the treatment arms.

The final analysis at 3.5 years from last randomization revealed a significant improvement in RFS with pembrolizumab compared with HDI or ipilimumab. The hazard ratio (HR) was 0.74 (99.62% CI, 0.57-0.96; P <.001).

On the other hand, pembrolizumab did not improve OS in the overall patient population (HR, 0.84; 96.3% CI, 0.62-1.13; P =.21) or among patients with PD-L1-positive biopsies at baseline (HR, 0.88; 97.8% CI, 0.60-1.29; P =.45).

The rate of treatment-related grade 3-5 adverse events (AEs) was lower with pembrolizumab (19.5%) than with HDI (71.2%) or ipilimumab (49.2%).

Fatal AEs in the pembrolizumab arm were myocarditis and acute leukemia. Fatal AEs in the ipilimumab group were colitis and pneumonitis. There were no fatal AEs in the HDI group.

“One year of adjuvant pembrolizumab improved relapse-free survival but not overall survival compared to high-dose interferon or ipilimumab in patients with high-risk resected melanoma,” Dr. Grossmann concluded. “Single-agent anti-PD-1 antibody treatment should be a standard of care option for adjuvant treatment of high-risk resected melanoma.”

Disclosures: This research was supported by the National Institutes of Health and Merck Sharp & Dohme Corp. Study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Grossmann KF, Othus M, Patel SP, et al. Final analysis of overall survival (OS) and relapse-free-survival (RFS) in the intergroup S1404 phase III randomized trial comparing either high-dose interferon (HDI) or ipilimumab to pembrolizumab in patients with high-risk resected melanoma.  J Clin Oncol. 2021;39:(suppl 15; abstr 9501). doi: 10.1200/JCO.2021.39.15_suppl.9501

This article originally appeared on Cancer Therapy Advisor