The phase III Checkmate 238 trial has shown improved recurrence-free survival with adjuvant nivolumab (Opdivo) vs ipilimumab (Yervoy) in patients with resected advanced melanoma. The findings were reported by Jeffrey Weber and colleagues in The New England Journal of Medicine.
In the double-blind trial, 906 patients aged ≥ 15 years undergoing complete resection of stage IIIB, IIIC, or IV melanoma from 130 sites in 25 countries were randomized between March 2015 and November 2015 to receive nivolumab at 3 mg/kg every 2 weeks (n = 453) or ipilimumab at 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n = 453). Treatment continued for up to 1 year or until disease recurrence or unacceptable toxicity. The primary endpoint was recurrence-free survival in the intention-to-treat population.
For the nivolumab vs ipilimumab groups: median age was 56 vs 54 years; 57% vs 59% were male; disease stage was IIIB in 36% vs 33%, IIIC in 45% vs 48%, and IV in 18% vs 19%; tumor programmed cell death ligand 1 (PD-L1) expression was < 5% in 61% vs 63% and ≥ 5% in 34% vs 34%; and 41% vs 43% had BRAF mutations.
Minimum follow-up was 18 months. The 12-month rate of recurrence-free survival was 70.5% in the nivolumab group vs 60.8% in the ipilimumab group (hazard ratio [HR] = 0.65, P < .001). The 12-month rate of recurrence-free survival was 64.3% vs 53.7% among patients with PD-L1 expression < 5% (HR = 0.71, 95% confidence interval [CI] = 0.56–0.91) and 81.9% vs 73.8% among those with PD-L1 expression ≥ 5% (HR = 0.50, 95% CI = 0.32–0.78). Recurrence-free survival benefit was observed in nearly all subgroups, including those defined by age, sex, disease stage, microscopic vs macroscopic nodal disease, ulceration status of primary tumor, and BRAF status.
Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the nivolumab group vs 45.9% of the ipilimumab group, with the most common in the ipilimumab group including diarrhea (9.5% vs 1.5%), increased alanine transaminase (5.7% vs 1.1%), and increased aspartate transaminase (4.2% vs 0.4%). Treatment was discontinued due to treatment-related adverse events in 30% of the ipilimumab group vs 3.5% of the nivolumab group.
The investigators concluded: “Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab.”
The study was funded by BMS and Ono Pharmaceutical. ■