Comparison of doxorubicin and cyclophosphamide (AC) versus single-agent paclitaxel (T) as adjuvant therapy for breast cancer in women with 0-3 positive axillary nodes: CALGB 40101

• Authors: Lawrence N. Shulman, Dana-Farber Cancer Institute; Donald A. Berry, Anderson Cancer Center, Houston; Constance T. Cirrincione, Duke University; Heather P. Becker, University of Chicago; Edith A. Perez, Mayo Clinic; Ruth O'Regan, Emory University; Silvana Martino, The Angeles Clinic and Research Institute; Charles L. Shapiro, Ohio State University; Charles J. Schneider, Christiana Healthcare Services; Gretchen Kimmick, Duke University; Harold J. Burstein, Dana-Farber Cancer Institute; Larry Norton, Memorial Sloan-Kettering Cancer Center; Hyman Muss, University of North Carolina at Chapel Hill; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center; Eric P. Winer, Dana-Farber Cancer Institute
• Journal Title: Journal of Clinical Oncology
• Volume: Volume 31, Number 15
• Publisher: American Society of Clinical Oncology | 2013-05-20, Pages 2311-2317
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1200/JCO.2013.53.7142
• Subjects: Health Sciences, Oncology; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology

Abstract

PURPOSE: Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity. PATIENTS AND METHODS: Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported. RESULTS: With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T. CONCLUSION: This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC.