Further evaluations of nivolumab (nivo) versus investigator’s choice (IC) chemotherapy for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CheckMate 141.
Authors: Robert L. Ferris, George R. Blumenschein, Jerome Fayette, Joel Guigay, A. Dimitrios Colevas, Lisa F. Licitra, Kevin J. Harrington, Stefan Kasper, Everett E. Vokes, Caroline Even, Francis P. Worden, Robert I. Haddad, Naomi Kiyota, Makoto Tahara, Manish Monga, Mark John Lynch, William J. Geese, Justin Kopit, James W Shaw, Maura L. Gillison
Journal: Journal of Clinical Oncology (2016)

6009 Background: Patients (pts) with R/M SCCHN have poor prognosis, and median OS for pts with platinum-refractory disease is ≤6 mo. We investigated if nivo, a fully human IgG4 anti-PD-1 mAb improves OS in pts with platinum-refractory R/M SCCHN compared to IC. Methods: Pts aged ≥18 yr with R/M SCCHN and ECOG PS 0–1 were randomized 2:1 to nivo 3 mg/kg q2w (until PD or toxicity) or single-agent IC (MTX, docetaxel, or cetuximab). The primary endpoint was OS; top line data were presented at AACR. Secondary endpoints included ORR and PFS (RECIST 1.1). Here we report additional endpoints: quality of life (QoL) assessments, correlative biomarkers, and safety. OS, PFS, and ORR were compared between treatment arms, by PD-L1 expression (≥1%, 5%, and 10%) and HPV (p16 IHC) status. Cellular and serum biomarkers are being evaluated. Pts aged ≥18 yr with R/M SCCHN and ECOG PS 0–1 were randomized 2:1 to nivo 3 mg/kg q2w (until PD or toxicity) or single-agent IC (MTX, docetaxel, or cetuximab). The primary endpoint was OS; top line data were presented at AACR. Secondary endpoints included ORR and PFS (RECIST 1.1). Here we report additional endpoints: quality of life (QoL) assessments, correlative biomarkers, and safety. OS, PFS, and ORR were compared between treatment arms, by PD-L1 expression (≥1%, 5%, and 10%) and HPV (p16 IHC) status. Cellular and serum biomarkers are being evaluated. Results: 361 pts were randomized, 240 to nivo and 121 to IC. A 30% reduction in risk of death was observed for nivo-treated pts with a median OS of 7.5 mo (95% CI: 5.5–9.1) for nivo and 5.1 mo (95% CI: 4.0–6.0) for IC. Among pts with PD-L1 ≥1% expression, median OS for nivo vs IC was 8.7 vs 4.6 mo in pts ≥1%, 8.8 vs 4.6 mo for ≥5%, and 8.7 vs 5.2 mo for ≥10%. Overall hazard ratio (HR) for OS of 0.70 (97.73% CI: 0.51–0.96) was consistently better for PD-L1 expression ≥1%: 0.56 (95% CI: 0.37–0.84), for ≥5%: 0.50 (95% CI: 0.30–0.83), and for ≥10%: 0.56 (95% CI: 0.31–0.99). Median PFS for nivo vs IC was 2.1 vs 2.0 mo (HR 0.64; 95% CI: 0.44–0.93) for PD-L1 ≥1%, 3.2 vs 2.0 mo (HR 0.53; 0.33–0.84) for ≥5%, and 2.1 vs 2.1 mo (HR 0.53; 0.31–0.88) for ≥10%. ORR for nivo with PD-L1 ≥1%, ≥5%, and ≥10% was 18.2%, 25.9%, and 32.6%, respectively, compared to 3.3%, 2.3%, and 2.9% for IC. Any grade treatment-related AEs (TRAEs) occurred in 59.3% and 77.5% of pts on nivo or IC, respectively. Grade 3/4 TRAEs occurred in 13.6% and 35.1% of pts. QoL and correlative biomarker data will be presented. Conclusions: Nivo demonstrated significant OS benefit compared to IC. OS and ORR improvement was greater with PD-L1 expression ≥1%. Nivo had a lower incidence of TRAEs compared to IC. Nivo is the first immune checkpoint inhibitor to demonstrate improved OS in a randomized controlled trial in R/M SCCHN. Clinical trial information: NCT02105636.