Journal Article
. 2013 Aug;31(26).
doi: 10.1200/JCO.2012.48.1275.

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 1 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  
Affiliations
  • PMID: 23940225
  •     13 References
  •     41 citations

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.

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