Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer
Abstract
PURPOSE Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer. METHODS Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)–negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test. RESULTS We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided P = .0747; 5-year OS 76.5% v 68.7%), but DFS was (HR, 0.75; one-sided P = .0168; 5-year DFS 71.7% v 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided P < .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided P = .3101). There were no grade 5 toxicities in either arm. CONCLUSION RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (44)
Pedro A. Torres-Saavedra
Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD
Stephen L. Breen
University of Toronto, Toronto, ON, Canada
Jason W. Chan
University of California, San Francisco, San Francisco, CA
Voichita Bar-Ad
Thomas Jefferson University Hospital, Philadelphia, PA
Greg Bednarz
University of Pittsburgh, Pittsburgh, PA
Daniel W. Bowles
University of Colorado Cancer Center, Aurora, CO
Stephen Breen
Barbara Burtness
Department of Internal Medicine and Yale Cancer Center, Yale School of Medicine, New Haven, CT
Arnab Chakravarti
James Cancer Hospital and Solove Research Institute, Columbus, OH
Jason Chan
Christine Chung
Moffitt Cancer Center, Tampa, FL
Anthony Cmelak
Vanderbilt University Medical Center, Nashville, TN
Adam P. Dicker
Jennifer Dorth
Case Western Reserve University, Cleveland, OH
Neal Dunlap
The James Graham Brown Cancer Center at University of Louisville, Louisville, KY
Adel El-Naggar
MD Anderson Cancer Center, Houston, TX
Clement K. Gwede
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Jonathan Harris
F. Christopher Holsinger
F. Christopher Holsinger, MD, FACS, Stanford University, Palo Alto, CA; Nofisat Ismaila, MD, MSc, American Society of Clinical Oncology (ASCO), Alexandria, VA; and Jamie A. Ku, MD, FACS, Cleveland Clinic, Cleveland, OH
Christopher U. Jones
Richard C. Jordan
NRG Oncology Biospecimen Bank, San Francisco, CA
Greg A. Krempl
Quynh-Thu Le
Stanford University School of Medicine, Stanford, CA
Nancy Lee
Memorial Sloan Kettering Cancer Center, New York, NY
Christopher Lominska
Daniel J. Ma
Mitchell Machtay
Loren K. Mell
UC San Diego Moores Cancer Center, La Jolla, CA
Phuc Felix Nguyen-Tân
CHUM—Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada
Harry Quon
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD
Adam Raben
Shyam Rao
University of California, Davis, Sacramento, CA
Stuart Samuels
David Sher
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX
Lillian L. Siu
Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto
Sharon Spencer
William A. Stokes
Emory University Hospital Midtown, Atlanta, GA
Vinita Takiar
Wade Thorstad
Washington University in St. Louis, St. Louis, MO
Pedro Torres-Saavedra
Christopher T. Wilke
Min Yao
Sue S. Yom
Department of Radiation Oncology University of California‐San Francisco San Francisco California USA
Melissa R. Young