• Robert L Ferris, Lisa Licitra, Jerome Fayette, Caroline Even, George Blumenschein, Kevin J Harrington, Joel Guigay, Everett E Vokes, Nabil F Saba, Robert Haddad, Shanmugasundaram Ramkumar, Jeffery Russell, Peter Brossart, Makoto Tahara, A Dimitrios Colevas, Fernando Concha-Benavente, Mark Lynch, Li Li, and Maura L Gillison.
• Departments of Otolaryngology and Immunology, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, Pennsylvania. ferrisrl@upmc.edu.
• Clin Cancer Res. 2019 Sep 1; 25 (17): 5221-5230.

PurposeCetuximab, which modulates immune responses, may affect the efficacy of subsequent immunotherapy. Here, we assessed outcomes with nivolumab, by prior cetuximab exposure, in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) who had experienced progression within 6 months of platinum-containing chemotherapy.Patients And MethodsIn the randomized, open-label, phase III CheckMate 141 trial, patients were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator's choice (IC) of single-agent chemotherapy, with stratification by prior cetuximab exposure. The primary endpoint was overall survival (OS); additional endpoints were progression-free survival, objective response rate, and safety.ResultsIn patients with prior cetuximab exposure, the median OS was 7.1 months with nivolumab versus 5.1 months with IC (HR, 0.84; 95% CI, 0.62-1.15); OS benefit with nivolumab was maintained across most demographic subgroups. In patients without prior cetuximab exposure, the median OS was 8.2 months with nivolumab versus 4.9 months with IC (HR, 0.52; 95% CI, 0.35-0.77); OS benefit with nivolumab was maintained across patient baseline subgroups including tumor programmed death ligand 1 (PD-L1) expression (<1% or ≥1%). Grade 3-4 treatment-related adverse event rates favored nivolumab versus IC in both subgroups.ConclusionsNivolumab appeared to improve efficacy versus IC regardless of prior cetuximab use, supporting its use in patients with R/M SCCHN with or without prior cetuximab exposure. The reduction in risk of death with nivolumab compared with IC was greater in patients without prior cetuximab exposure versus with prior cetuximab exposure.©2019 American Association for Cancer Research.

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