Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial

• Type of Material: Article
• Authors: Suzanne L Topalian, Johns Hopkins Bloomberg Kimmel Inst Canc Immunoth; Shailender Bhatia, University of Washington; Asim Amin, Atrium Healthcare; Ragini Kudchadkar, Emory University; William H Sharfman, Johns Hopkins Bloomberg Kimmel Inst Canc Immunoth; Celeste Lebbé, Université de Paris; Jean-Pierre Delord, Institut Claudius Regaud; Lara A Dunn, Memorial Sloan Kettering Cancer Center; Michi M Shinohara, University of Washington; Rima Kulikauskas, University of Washington; Christine H Chung, H. Lee Moffitt Cancer Center and Research Institute; Uwe M Martens, SLK-Clinics, MOLIT Institute, Heilbronn; Robert L Ferris, University of Pittsburgh; Julie E Stein, Johns Hopkins Bloomberg Kimmel Inst Canc Immunoth; Elizabeth L Engle, Johns Hopkins Bloomberg Kimmel Inst Canc Immunoth; Lot A Devriese, University Medical Center Utrecht; Christopher D Lao, University of Michigan; Junchen Gu, Bristol Myers Squibb; Bin Li, Bristol Myers Squibb; Tian Chen, Bristol Myers Squibb; Adam Barrows, Bristol Myers Squibb; Andrea Horvath, Bristol Myers Squibb; Janis M Taube, Johns Hopkins Bloomberg Kimmel Inst Canc Immunoth; Paul Nghiem, University of Washington
• Language: English
• Date: 2020-08-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by American Society of Clinical Oncology
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.20.00201
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 38
• Issue: 22
• Start Page: 2476
• End Page: +
• Grant/Funding Information: Supported by Bristol Myers Squibb and ONO Pharmaceutical Company Limited (CheckMate 358 study); by The Mark Foundation for Cancer Research and National Cancer Institute R01 CA142779 (J.M.T.; multispectral immunofluorescence tissue staining and analysis at the Johns Hopkins Bloomberg∼Kimmel Institute for Cancer Immunotherapy); and by P30-CA015704 and P01-CA225517 (P.N.).
• Keywords: Science & Technology; EXPRESSION; ANTIBODIES; Oncology; CHEMOTHERAPY; Life Sciences & Biomedicine; POLYOMAVIRUS
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

PURPOSE Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer commonly driven by the Merkel cell polyomavirus (MCPyV). The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunosuppressive pathway is often upregulated in MCC, and advanced metastatic MCC frequently responds to PD-1 blockade. We report what we believe to be the first trial of anti-PD-1 in the neoadjuvant setting for resectable MCC. METHODS In the phase I/II CheckMate 358 study of virus-associated cancer types, patients with resectable MCC received nivolumab 240 mg intravenously on days 1 and 15. Surgery was planned on day 29. Tumor regression was assessed radiographically and microscopically. Tumor MCPyV status, PD-L1 expression, and tumor mutational burden (TMB) were assessed in pretreatment tumor biopsies. RESULTS Thirty-nine patients with American Joint Committee on Cancer stage IIA-IV resectable MCC received $ 1 nivolumab dose. Three patients (7.7%) did not undergo surgery because of tumor progression (n 5 1) or adverse events (n 5 2). Any-grade treatment-related adverse events occurred in 18 patients (46.2%), and grade 3-4 events in 3 patients (7.7%), with no unexpected toxicities. Among 36 patients who underwent surgery, 17 (47.2%) achieved a pathologic complete response (pCR). Among 33 radiographically evaluable patients who underwent surgery, 18 (54.5%) had tumor reductions $ 30%. Responses were observed regardless of tumor MCPyV, PD-L1, or TMB status. At a median follow-up of 20.3 months, median recurrence-free survival (RFS) and overall survival were not reached. RFS significantly correlated with pCR and radiographic response at the time of surgery. No patient with a pCR had tumor relapse during observation. CONCLUSION Nivolumab administered approximately 4 weeks before surgery in MCC was generally tolerable and induced pCRs and radiographic tumor regressions in approximately one half of treated patients. These early markers of response significantly predicted improved RFS. Additional investigation of these promising findings is warranted.