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.

Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 1007)
Lawrence N. Shulman, Donald A. Berry, Constance T. Cirrincione, Heather Becker, Edith A. Perez, Ruth O'Regan, Silvana Martino, Charles L. Shapiro, James Atkins, Charles Schneider, Gretchen Genevieve Kimmick, Harold J. Burstein, Larry Norton, Hyman Bernard Muss, Clifford Hudis, Eric P. Winer, Cancer and Leukemia Group B; Dana-Farber Cancer Institute, Boston, MA; The University of Texas MD Anderson Cancer Center, Houston, TX; Duke Cancer Institute Biostatistics, Durham, NC; University of Chicago, Chicago, IL; Mayo Clinic, Jacksonville, FL; Georgia Cancer Center for Excellence at Grady Memorial Hospital, Atlanta, GA; The Angeles Clinic and Research Institute, Santa Monica, CA; The Ohio State University, Columbus, OH; Southeastern Medical Oncology Center, Goldsboro, NC; Christiana Care Health System, Newark, DE; Duke Cancer Institute, Durham, NC; Memorial Sloan-Kettering Cancer Center, New York, NY; University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC

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Abstract Disclosures


Background: Determining optimal adjuvant chemotherapy for early stage breast cancer depends on efficacy and toxicity. We sought to determine if T is equivalent to AC but with reduced toxicity. Methods: Pts with operable breast cancer with 0-3 positive nodes were enrolled on a 2x2 factorial design study which addressed (1) superiority of 6 vs. 4 cycles of therapy (previously reported, Shulman, JCO 2012) and (2) equivalence of single-agent T to standard AC, defined as upper bound of 95% confidence interval (CI) of hazard ratio (HR) of T vs. AC < 1.30 for the primary endpoint of relapse-free survival (RFS). A planned target of 567 RFS events required 4,646 pts with 4 yrs FU. At activation in 2002, T (80mg/m2) was q1wk for 12 or 18 wks and AC (60/600 mg/m2) was q3wk for 4 or 6 cycles. In 2003 (570 pts enrolled) schedules were revised to 4 or 6 cycles q2wk for both T (175 mg/m2) and AC. The 6-cycle arms were dropped in 2008 (3,171 pts enrolled) due to slow accrual. Relative effectiveness of T to AC is shown by hazard ratio (HR). Logrank p-values are measures of discordance but are not relevant for the equivalence question and are not adjusted for multiple comparisons. Results: After enrolling 3,871 pts, the study closed in 2010 due to slowing accrual. With a median follow-up of 6.1 yrs there are 437 RFS events. The HR of 1.26 (95% CI: 1.05-1.53; p = 0.02) does not allow a conclusion of equivalence of T with AC. With 266 deaths the HR for overall survival (OS) is 1.27 (95% CI=1.00-1.62; p = 0.05), favoring AC. The estimated absolute advantage of AC at 5 yrs is 3% (91 vs. 88%) for RFS and 1% (95 vs. 94%) for OS. All 9 treatment-related deaths were in pts receiving AC and are included in the survival analysis. The incidence of Grade 3+ toxicity for AC vs T was 33% vs. 4% for hematologic toxicity and 36% vs 22% for non-hematologic toxicity. Conclusions: This trial did not show equivalence of T to AC, a conclusion that is very unlikely to change with additional follow-up. T was less toxic than AC. Clinical trial information: NCT00041119.