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.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Sandra M. Swain, Gong Tang, Charles E. Geyer Jr, 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, Soonmyung Paik, Joseph P. Costantino, Eleftherios P. Mamounas, and Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project (NSABP); Norman Wolmark, Allegheny General Hospital, Allegheny Health Network; Gong Tang and Joseph P. Costantino, NSABP Biostatistical Center and University of Pittsburgh Graduate School of Public Health; Priya Rastogi, University of Pittsburgh Cancer Institute; Adam M. Brufsky, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Charles E. Geyer Jr, Virginia Commonwealth University, Richmond, VA; James N. Atkins, Southeast Cancer Control Consortium-Community Clinical Oncology Program, Goldsboro; Edward A. Levine, Wake Forest University, Winston-Salem, NC; Paul P. Donnellan, University Hospital, Galway, and the All-Ireland Cooperative Oncology Research Group, Dublin, Ireland; Louis Fehrenbacher, Kaiser Permanente Northern California, Vallejo; Jonathan A. Polikoff, Kaiser Permanente Southern California, San Diego, CA; Catherine A. Azar, Kaiser Permanente, Denver, CO; André Robidoux, Centre hopitalier de l'Université de Montréal (CHUM), Montréal; Louise Provencher, CHU de Québec, Hôpital du Saint-Sacrement, Québec City, QC, Canada; David D. Biggs, Helen F. Graham Cancer Center, Christiana Care Health System, Newark, DE; John L. Zapas, Medstar Franklin Square Medical Center, Baltimore, MD; Donald W. Northfelt, Mayo Clinic Arizona, Scottsdale, AZ; and Eleftherios P. Mamounas, MD Anderson Cancer Center, Orlando, FL.
Sandra M
SM
Swain
Gong
G
Tang
Charles E
CE
Geyer
Priya
P
Rastogi
James N
JN
Atkins
Paul P
PP
Donnellan
Louis
L
Fehrenbacher
Catherine A
CA
Azar
André
A
Robidoux
Jonathan A
JA
Polikoff
Adam M
AM
Brufsky
David D
DD
Biggs
Edward A
EA
Levine
John L
JL
Zapas
Louise
L
Provencher
Donald W
DW
Northfelt
Soonmyung
S
Paik
Joseph P
JP
Costantino
Eleftherios P
EP
Mamounas
Norman
N
Wolmark
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
D043823:Taxoids; D003841:Deoxycytidine; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D000093542:Gemcitabine