Aims:
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.
Methods:
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.
Results:
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.
Conclusions:
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.