Aims:
In the phase 3 CheckMate 141 trial, nivolumab demonstrated superior overall survival (OS) and better tolerability in patients with R/M SCCHN vs IC. Patients with SCCHN progressing within 6 months of platinum in the primary setting have dismal prognosis. We report on patients who were platinum refractory in the primary setting, and updated results overall.
Methods:
Patients (N=361) with platinum-refractory R/M SCCHN were randomized 2:1 to nivolumab 3mg/kg Q2W or weekly IC (methotrexate/docetaxel/cetuximab). Primary endpoint was OS estimated by Kaplan-Meier. Cox proportional hazards models were used to estimate HRs and CIs. Additional endpoints: objective response rate (ORR), safety. Outcomes were analyzed overall and post-hoc in patients who were platinum-refractory in the primary setting (received nivolumab/IC as first-line R/M therapy).
Results:
Characteristics of patients who received nivolumab (n=52) or IC (n=26) as first-line R/M therapy were similar to the overall population. Nivolumab significantly improved OS vs IC among first-line R/M patients (median [95%CI]: 7.7 months [3.1-13.8] vs 3.3 months [2.1-6.4]; HR [95%CI]=0.56 [0.33-0.95]); 12-month OS rate: 39.2% vs 15.4%; ORR 19.2% vs 11.5%. At 11.4-months minimum follow-up, updated results overall were similar to the initial analysis. Median OS (95%CI) was 7.7 months (5.7-8.8) for nivolumab vs 5.1 months (4.0-6.2) for IC; HR (95%CI)=0.71 (0.55-0.90); P=0.0048. For nivolumab vs IC, 18-month OS rate: 21.5% vs 8.3%; ORR: 13.3% vs 5.8%. Nivolumab doubled median duration of response (9.7 vs 4.0 months). Grade 3–4 treatment-related adverse event rates for nivolumab vs IC: 15.3% vs 36.0% (overall); 27.5% vs 32.0% (first-line R/M); no new deaths occurred due to study drug.
Conclusions:
Nivolumab significantly improved OS and increased ORR vs IC in a first-line R/M subgroup, supporting its use as first-line therapy for patients with platinum-refractory R/M SCCHN. Nivolumab showed significant survival benefit and better tolerability vs IC in patients with platinum-refractory R/M SCCHN.