Nivolumab in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: Efficacy and Safety in CheckMate 141 by Prior Cetuximab Use

• Type of Material: Article
• Authors: Robert L. Ferris, University of Pittsburgh; Lisa Licitra, Fondazione IRCCS Istituto Nazionale dei Tumori; Jerome Fayette, Centre Leon Berard; Caroline Even, Gustave Roussy; George Blumenschein, Jr., The University of Texas MD Anderson Cancer Center; Kevin J. Harrington, Royal Marsden/The Institute of Cancer Research; Joel Guigay, Université Côte d'Azur; Everett E. Vokes, University of Chicago; Nabil Saba, Emory University; Robert Haddad, Dana-Farber/Harvard Cancer Center; Shanmugasundaram Ramkumar, University Hospital Southampton/NHS Foundation Trust; Jeffery Russell, H. Lee Moffitt Cancer Center & Research Institute; Peter Brossart, University Hospital of Bonn; Makoto Tahara, National Cancer Center Hospital East; A. Dimitirios Colevas, Stanford University; Fernando Concha-Benavente, University of Pittsburgh; Mark Lynch, Bristol-Myers Squibb; Li Li, Bristol-Myers Squibb; Maura L. Gillison, The University of Texas MD Anderson Cancer Center
• Language: English
• Date: 2019-09-01
• Publisher: AMER ASSOC CANCER RESEARCH
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2019
• Final Published Version (URL): http://dx.doi.org/10.1158/1078-0432.CCR-18-3944
• Title of Journal or Parent Work: CLINICAL CANCER RESEARCH
• Volume: 25
• Issue: 17
• Start Page: 5221
• End Page: 5230
• Grant/Funding Information: Professional medical writing assistance was provided by Beth Burke, PhD, CMPP, and Meenakshi Subramanian, PhD, CMPP, of Evidence Scientific Solutions, and was funded by Bristol-Myers Squibb. K.J. Harrington acknowledges support from the Royal Marsden/the Institute of Cancer Research, National Institute of Health Research Biomedical Research Centre, and Oracle Cancer Trust. Dr. Ferris and his laboratory research effort are supported by the NIH grants, P50 CA097190–14, P30 CA047904–28, and R01 CA206517. The University of Texas MD Anderson Cancer Center is supported by the NIH (grant P30 CA016672). This study was funded by Bristol-Myers Squibb.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
• Keywords: THERAPY; CORRELATE; Life Sciences & Biomedicine; INVESTIGATORS CHOICE; Oncology; IMMUNITY; CHEMOTHERAPY; Science & Technology; EGFR
• Research Categories: Engineering, Biomedical; Health Sciences, Oncology; Health Sciences, Immunology

Abstract

Purpose: Cetuximab, 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 platinumcontaining chemotherapy. Patients and Methods: In 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. Results: In 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. Conclusions: Nivolumab 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.