In an analysis from the phase III CheckMate 238 trial reported in the Journal of Clinical Oncology, Jeffrey Weber, MD, PhD, and colleagues found that progression-free and overall survival were improved with subsequent systemic therapy following late vs early recurrence with adjuvant nivolumab in patients with resected stage IIIB–C or IV melanoma.
Jeffrey Weber, MD, PhD
Study Details
In CheckMate 238, patients were randomly assigned to receive nivolumab at 3 mg/kg every 2 weeks or ipilimumab at 10 mg/kg every 3 weeks for four doses and then every 12 weeks for either 1 year or until disease recurrence or unacceptable toxicity. Adjuvant nivolumab significantly improved recurrence-free survival vs ipilimumab, with no significant difference in overall survival being observed.
The current analysis investigated outcomes with subsequent systemic therapy following early (≤ 12 months) and late (> 12 months) disease recurrence on nivolumab. Subsequent systemic therapy included anti–PD-L1/PD-1 monotherapy, anti–CTLA-4 monotherapy, anti–CTLA-4 plus anti–PD-1 therapy, BRAF/MEK inhibitors, and chemotherapy.
Key Findings
Recurrence was observed in 198 (44%) of 453 patients in the nivolumab group, including 122 with early and 76 with late recurrence. Median progression-free survival after start of subsequent systemic therapy was 4.7 months among those with early recurrence vs 12.4 months among those with late recurrence; 24-month rates were 16% vs 31%, respectively. Median overall survival was 19.8 months vs 42.8 months, with 24-month rates of 37% vs 73%, respectively.
Patients with late vs early recurrence on nivolumab were more likely to benefit from anti–PD-L1/PD-1 monotherapy, with 12- and 24-month progression-free survival rates of 50% vs 17% and 35% vs 8%, respectively, and 12- and 24-month overall survival rates of 80% vs 67% and 71% vs 17%, respectively.
Nivolumab-treated patients with early recurrence had better 24-month overall survival with anti–CTLA-4 monotherapy (50%), anti–CTLA-4 plus anti–PD-1 therapy (43%), and BRAF/MEK inhibitor therapy (39%) compared with anti–PD-L1/PD-1 monotherapy (17%).
The investigators concluded, “Postrecurrence survival was longer for patients who recurred > 12 months. Patients on nivolumab who recurred early benefitted from subsequent systemic therapy but had better survival with ipilimumab-based regimens or targeted therapy compared with anti–PD-1 monotherapy.”
Dr. Weber, of the Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and Ono Pharmaceutical Company Ltd. For full disclosures of the study authors, visit ascopubs.org.
