Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: The NSABP B-38 trial

Sandra M. Swain, Gong Tang, Charles E. Geyer, Priya Rastogi, James N. Atkins, Paul P. Donnellan, Louis Fehrenbacher, Catherine A. Azar, André Robidoux, Jonathan A. Polikoff, Adam M. Brufsky, David D. Biggs, Edward A. Levine, John L. Zapas, Louise Provencher, Donald W. Northfelt, Soonmyung Paik, Joseph P. Costantino, Eleftherios P. Mamounas, Norman Wolmark

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Abstract

Purpose: Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. Patients and Methods: We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. Results: There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Conclusion: Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.

Original languageEnglish (US)
Pages (from-to)3197-3204
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number26
DOIs
StatePublished - Sep 10 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Swain, S. M., Tang, G., Geyer, C. E., Rastogi, P., Atkins, J. N., Donnellan, P. P., Fehrenbacher, L., Azar, C. A., Robidoux, A., Polikoff, J. A., Brufsky, A. M., Biggs, D. D., Levine, E. A., Zapas, J. L., Provencher, L., Northfelt, D. W., Paik, S., Costantino, J. P., Mamounas, E. P., & Wolmark, N. (2013). Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: The NSABP B-38 trial. Journal of Clinical Oncology, 31(26), 3197-3204. https://doi.org/10.1200/JCO.2012.48.1275