Radiotherapy plus Cetuximab for Squamous Cell Carcinoma of the Head and
Neck
James A. Bonner, M.D., Paul M. Harari, M.D., Jordi Giralt, M.D., Nozar Azarnia, Ph.D., Dong M. Shin,M.D., Roger B. Cohen, M.D., Christopher U. Jones, M.D., Ranjan Sur, M.D., Ph.D., David Raben, M.D., Jacek Jassem, M.D., Ph.D., Roger Ove, M.D., Ph.D., MerrillS. Kies, M.D., Jose Baselga, M.D., Hagop Youssoufian, M.D., Nadia Amellal, M.D., Eric K. Rowinsky, M.D., and K. Kian Ang, M.D., Ph.D.
New England Journal of Medicine 2006; 354:567-578, Feb 9,2006
ABSTRACT
Background: We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of loco regionally advanced squamous cell carcinoma of the head and neck.
Methods: Patients with loco regionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of loco regional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety.
Results: The median duration of loco regional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radio therapy alone (hazard ratio for loco regional progression or death, 0.68; P=0.005). With a median follow-up of 54.0 months, the median duration of overall survival was49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P=0.03).Radiotherapy plus cetuximab significantly prolonged progression-free survival(hazard ratio for disease progression or death, 0.70; P=0.006). With the exception of acne i form rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups.
Conclusions: Treatment of loco regionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves loco regional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227[ClinicalTrials.gov] .)
Source
Information
From the Department of Medicine, University of Alabama, Birmingham (J.A.B., R.O.); the Department of Human Oncology, University of Wisconsin, Madison (P.M.H.); the Services of Radiation Oncology (J.G.) and Oncology (J.B.), Vall d'Hebron University Hospital, Barcelona; ImClone Systems, New York (N.A., H.Y., E.K.R.); the Divisions of Cancer Medicine (D.M.S.,M.S.K.) and Radiation Oncology (K.K.A.), University of Texas M.D. Anderson Cancer Center, Houston; the Department of Medicine, University of Virginia, Charlottesville (R.B.C.); Radiological Associates of Sacramento, Sacramento, Calif. (C.U.J.); the Department of Radiation Oncology; University of Witwatersrand, Johannesburg (R.S.); the Department of Radiation Oncology, University of Colorado, Aurora (D.R.); the Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland (J.J.); and Merck, Darmstadt, Germany (N.A.).
Address reprint requests to Dr. Rowinsky at ImClone Systems,33 ImClone Dr., Branchburg, NJ 08876, or at eric.rowinsky@imclone.com.
Phase III Randomized Trial of Cisplatin Plus Placebo Compared With Cisplatin Plus Cetuximab in Metastatic/Recurrent Head and Neck Cancer: An Eastern Cooperative Oncology Group Study
Barbara Burtness, Meredith A. Goldwasser, William Flood, Bassam Mattar, Arlene A. Forastiere
Journal of Clinical Oncology, Vol 23, No 34(December 1), 2005: pp. 8646-8654
Address reprint requests to Barbara Burtness, MD, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111; e-mail: barbara.burtness@fccc.edu
PURPOSE: Therapy of recurrent/metastatic squamous cell carcinoma of the head and neck results in median progression-free survival (PFS) of 2 months. These cancers are rich in epidermal growth factor receptor (EGFR). We wished to determine whether the addition of cetuximab, which inhibits activation of EGFR, would improve PFS.
PATIENTS AND METHODS: Patients with recurrent/metastatic squamous cell carcinoma of the head and neck were randomly assigned to receive cisplatin every 4 weeks, with weekly cetuximab(arm A) or placebo (arm B). Tumor tissue was assayed for EGFR expression by immunohistochemistry. The primary end point was PFS. Secondary end points of interest were response rate, toxicity, overall survival, and correlation of EGFR with clinical end points.
RESULTS: There were 117analyzable patients enrolled. Median PFS was 2.7 months for arm B and 4.2months for arm A. The hazard ratio for progression of arm A to arm B was 0.78(95% CI, 0.54 to 1.12). Median overall survival was 8.0 months for arm B and9.2 months for arm A (P = .21). The hazard ratio for survival by skin toxicity in cetuximab-treated patients was 0.42 (95% CI, 0.21 to 0.86). Objective response rate was 26% for arm A and 10% for arm B (P = .03). Enhancement of response was greater for patients with EGFR staining present in less than 80%of cells.
CONCLUSION: Addition of cetuximab to cisplatin significantly improves response rate. There was a survival advantage for the development of rash. Progression-free and overall survival were not significantly improved by the addition of cetuximab in this study.
Supported in part by Public Health Service Grants No. CA23318, CA66636, CA21115, CA07190, and CA16116 from the National Cancer Institute, National Institutes of Health, and the United States Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
Presented in part at the 38thAnnual Meeting of the American Society of Clinical Oncology, May 18-21,Orlando, FL, and the American Association for Cancer Research/National Cancer Institute/European Organization for Research and Treatment of Cancer International Conference on Molecular Targets in Cancer Therapy, November17-21, 2003, Boston, MA