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

• Published in: Journal of clinical oncology Vol. 31; no. 26; pp. 3197 - 3204
• Main Authors: SWAIN, Sandra M, GONG TANG, BRUFSKY, Adam M, BIGGS, David D, LEVINE, Edward A, ZAPAS, John L, PROVENCHER, Louise, NORTHFELT, Donald W, PAIK, Soonmyung, COSTANTINO, Joseph P, MAMOUNAS, Eleftherios P, WOLMARK, Norman, GEYER, Charles E, RASTOGI, Priya, ATKINS, James N, DONNELLAN, Paul P, FEHRENBACHER, Louis, AZAR, Catherine A, ROBIDOUX, André, POLIKOFF, Jonathan A
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.09.2013
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Chemotherapy, Adjuvant; Cyclophosphamide - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Doxorubicin - administration & dosage; Drug Therapy, Combination; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor - therapeutic use; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Invasiveness; ORIGINAL REPORTS; Paclitaxel - administration & dosage; Prognosis; Survival Rate; Taxoids - administration & dosage; Tumors; Phase III trial; Human; Breast disease; Adjuvant treatment; Breast cancer; Malignant tumor; Mammary gland diseases; Chemotherapy; Treatment; Cancerology; Adult; Clinical trial; Female; Woman; Therapeutic protocol; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2012.48.1275

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. 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. 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). 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.