In CheckMate 141, nivolumab resulted in significantly prolonged overall survival (OS), favorable safety, and stable quality of life vs IC in patients with platinum-refractory R/M SCCHN. Cetuximab, a formal trial stratification factor, permits exploratory subgroup assessment. Outcomes by prior cetuximab are described.
CheckMate 141 was a randomized, open-label, phase 3 trial (NCT02105636). Patients (N=361) with platinum-refractory R/M SCCHN were randomized 2:1 (stratified by prior cetuximab) to nivolumab 3mg/kg every 2 weeks or IC (methotrexate/docetaxel/cetuximab). Primary endpoint was OS; additional endpoints: progression-free survival (PFS), objective response rate (ORR), safety. Multivariate analysis explored influence of additional factors.
In the nivolumab and IC arms, respectively, 93 and 47 patients had no prior cetuximab use, and 147 and 74 received prior cetuximab. Median OS (95%CI) for nivolumab vs IC without: 8.1 (5.3-12.7) vs 4.7 (3.0-7.2) months (HR [95%CI]=0.55 [0.35-0.86]) and with prior cetuximab: 6.9 (4.9-8.8) vs 5.2 (4.1-6.8) months (HR [95%CI]=0.81 [0.57-1.15]). Median OS was longer for nivolumab vs IC in patients with tumor PD-L1 expression ≥1% regardless of prior cetuximab, and in patients with PD-L1 expression <1% without prior cetuximab. ORR for nivolumab vs IC was 17.2% vs 4.3% without and 10.9% vs 6.8% with prior cetuximab. ORR for nivolumab vs IC among PD-L1 ≥1% was 19.4% vs 0% without and 15.4% vs 2.5% with prior cetuximab. ORR for nivolumab vs IC among HPV+: 29.6% vs 0% without and 5.6% vs 5.6% with prior cetuximab. PFS was similar regardless of prior cetuximab. Grade 3–4 treatment-related adverse event rates for nivolumab vs IC: 11.7% vs 40.9% with; 15.4% vs 26.7% without prior cetuximab.
OS and ORR improved with nivolumab vs IC regardless of prior cetuximab; magnitude of benefit was greater in patients without prior cetuximab exposure. These results support use of nivolumab for R/M SCCHN regardless of prior cetuximab.