OT1-02-07: NSABP B-47: A Randomized Phase III Trial of Adjuvant Therapy Comparing Chemotherapy Alone (Six Cycles of Docetaxel Plus Cyclophosphamide or Four Cycles of Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel) to Chemotherapy Plus Trastuzumab in Women with Node-Positive or High-Risk Node-Negative HER2−Low Invasive Breast Cancer.

Abstract

Abstract Adjuvant studies utilizing trastuzumab in early HER2+ breast cancer demonstrated a large reduction in recurrence and death. Post-enrollment central testing showed HER2 non-amplified participants derived similar benefit. Among HER2−amplified patients, multiple studies showed no effect on benefit by degree of amplification. Extensive testing including blinded external review confirmed the non-amplified nature of the HER2 normal group. Detailed relevant background and confirmatory studies will be provided. As a result of these findings, NSABP study B-47, sponsored by the NCI, was activated January 2011. The study is NCI central IRB approved, open in the CTSU, and endorsed by SWOG as of April 2011. Study: Selection of one of the two chemotherapy regimens is by physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) administered IV every 3 weeks for 6 cycles; the anthracycline regimen is AC followed by WP (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered IV either every 3 weeks or every 2 weeks [per investigator discretion] for 4 cycles followed by paclitaxel 80 mg/m2 IV weekly for 12 doses). Patients will be randomly assigned to receive chemotherapy with or without trastuzumab therapy. For patients receiving the TC chemotherapy regimen, trastuzumab will be given every 3 weeks during and following chemotherapy until 1 year after the first trastuzumab dose (8 mg/kg loading dose; 6 mg/kg for the remaining doses). For patients receiving the AC followed by WP chemotherapy regimen, trastuzumab will begin with the first dose of weekly paclitaxel and will be given weekly for 12 doses (4 mg/kg loading dose; 2 mg/kg for the remaining weekly doses). Following completion of WP, trastuzumab therapy will continue with 6 mg/kg doses given every 3 weeks for a total of 1 year. Patients will also receive adjuvant radiation therapy and endocrine therapy, as clinically indicated. Detailed menstrual history, concurrent medications, weight changes, and biomarkers (estrogen, stress, inflammation status) will be collected throughout the study. Collection of circulating tumor cells as an ancillary study is planned. Eligibility: Eligibility includes: node positive or high risk node negative female breast cancer patients; HER2 IHC 1+ or 2+ scores, but non amplified by FISH; normal cardiac, renal, and liver function. Detailed eligibility will be provided. Statistical: The primary aim is to determine whether the addition of trastuzumab to chemotherapy improves invasive disease-free survival (IDFS). 3260 patients will be enrolled to provide statistical power of 0.9 to detect a 33% reduction in the hazard rate of IDFS using a one-sided alpha level of 0.025. Projected accrual time is approximately 3 years. Progress: Protocol was activated in January 2011. First patient was entered in February 2011. As of June 16, 2011, 115 of 3260 patients have been enrolled. Supported by NCI U10-12027, -37377, 69651, 69974, and Genentech, Inc. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-07.