Cetuximab plus chemoradiotherapy in immunocompetent patients with anal carcinoma: A phase II Eastern cooperative oncology group-American college of radiology imaging network cancer research group trial (E3205)

• Type of Material: Article
• Authors: Madhur K. Garg, Albert Einstein College of Medicine; Fengmin Zhao, Dana-Farber Cancer Institute; Joseph A. Sparano, Albert Einstein College of Medicine; Joel Palefsky, University of California; Richard Whittington, VA Medical Center; Edith P. Mitchell, Thomas Jefferson University; Mary F. Mulcahy, Northwestern University; Karin I. Armstrong, Cancer Center of Kansas; Nassim H. Nabbout, Emory University; Shalom Kalnicki, Albert Einstein College of Medicine; Bassel El-Rayes, Emory University; Adedayo A. Onitilo, Overlook Medical Center; Daniel J. Moriarty, Quality Assurance Review Center; Thomas J. Fitzgerald, Quality Assurance Review Center; Al B. Benson, United Hospital
• Language: English
• Date: 2017-03-01
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2017 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2016.69.1667
• Title of Journal or Parent Work: Journal of Clinical Oncology
• ISSN: 0732-183X
• Volume: 35
• Issue: 7
• Start Page: 718
• End Page: 726
• Grant/Funding Information: The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.; This study was coordinated by the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants No. CA23318, CA66636, CA21115, CA180820, CA180794, CA14958, CA189859, CA15488, CA13650, CA17145, CA35267, CA189863, CA35431, CA189808, CA180864, CA35412, CA189956, and CA107868; the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services; Grant No. U10 CA029511 from the Quality Assurance Radiotherapy Committee; and Grant No. U24 CA180803 from the Imaging and Radiation Oncology Core.; Research Funding: Genentech, Gilead Sciences, Amgen, Astellas Pharma, Bayer/Onyx Pharmaceuticals, Novartis, Alchemia, AVEO Pharmaceuticals, Infinity Pharmaceuticals, Merck Sharp & Dohme
• Keywords: Carcinoma, Squamous Cell; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Fluorouracil; Cetuximab; Immunocompetence; Humans; Middle Aged; Anus Neoplasms; Neoplasm Staging; Adult; Cisplatin; Female; Survival Rate; Disease-Free Survival; Aged; Male
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight onceweekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided a, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.