Duration of adjuvant chemotherapy for stage III colon cancer

Grothey, A. et al. (2018) Duration of adjuvant chemotherapy for stage III colon cancer. New England Journal of Medicine, 378(13), pp. 1177-1188. (doi: 10.1056/NEJMoa1713709) (PMID:29590544) (PMCID:PMC6426127)

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BACKGROUND Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12. RESULTS After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority). CONCLUSIONS Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.)

Item Type:Articles
Additional Information:Comment: A New IDEA in Adjuvant Chemotherapy for Colon Cancer by Richard L. Schilsky, M.D. Published in New England Journal of Medicine 378:1242-1244. http://dx.doi.org/10.1056/NEJMe1800419
Glasgow Author(s) Enlighten ID:Paul, Mr James
Authors: Grothey, A., Sobrero, A. F., Shields, A. F., Yoshino, T., Paul, J., Taieb, J., Souglakos, J., Shi, Q., Kerr, R., Labianca, R., Meyerhardt, J. A., Vernerey, D., Yamanaka, T., Boukovinas, I., Meyers, J. P., Renfro, L. A., Niedzwiecki, D., Watanabe, T., Torri, V., Saunders, M., Sargent, D. J., Andre, T., and Iveson, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:New England Journal of Medicine
Publisher:Massachusetts Medical Society
ISSN (Online):1533-4406
Copyright Holders:Copyright © 2018 Massachusetts Medical Society
First Published:First published in New England Journal of Medicine 378(13):1177-1188
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
615371Cancer Research UK Clinical Trials Unit - Core Programme FundingRobert JonesCancer Research UK (CRUK)15960RI CANCER SCIENCES