SAN ANTONIOThe first interim results from the BCIRG 006 phase III trial showed that trastuzumab (Herceptin) combined with docetaxel (Taxotere)-based regimens significantly improved disease-free survival (DFS) in early HER2-positive breast cancer. Genetic studies further delineated a subgroup of patients for whom truly targeted therapy may be applied in the future. Dennis Slamon, PhD, MD, co-chair of the Breast Cancer International Research Group (BCIRG) 006 adjuvant study and director of clinical and translational research at UCLA's Jonsson Comprehensive Cancer Center, presented the 23-month follow-up data at the 28th Annual San Antonio Breast Cancer Symposium (abstract 1).
"Both the experimental arms containing trastuzumab significantly exceeded the control arm in terms of efficacy," Dr. Slamon said. Importantly, he added, since cardiotoxicity is a concern with trastuzumab, the non-anthracycline-containing regimen reduced the risk of recurrence without increasing cardiotoxicity.
Dr. Slamon also presented exciting new findings regarding "coamplification" of the HER2 gene and the topoisomerase II-α gene (TOPO II-α), which is the target of anthracyclines. Patients who had amplification of both these genes had the best outcomes with trastuzumab plus anthracycline. "We just got these data on Thursday night. It's hot off the press," Dr. Slamon said. "I think that others will want to repeat these data, but we are pretty confident that this is correct."
The BCIRG 006 study was designed to evaluate how to potentially maximize efficacy of trastuzumab-based therapy in the adjuvant treatment of HER2-positive breast cancer, while minimizing toxicity. In particular, investigators aimed to determine if the increased toxicity seen with the combination of trastuzumab and doxorubicin could be avoided using a novel non-anthracycline-containing regimen that has demonstrated activity preclinically. Docetaxel was used in the regimen, rather than paclitaxel, based on preclinical evidence indicating an interaction with trastuzumab, he said.
The adjuvant study included 3,222 women with FISH-positive HER2-overexpressing tumors who were node-positive or otherwise at high risk for recurrence. Approximately half had received hormonal therapy and over half received mastectomy and radiotherapy. Patient groups were well balanced among arms.
Patients were randomized to receive one of the following regimens:
- Standard treatment with four cycles of doxorubicin and cyclophosphamide (60/600 mg/m2), followed by docetaxel 100 mg/m2 for four cycles (AC→T) (n = 1,073).
- Experimental treatment with the above regimen together with 1 year of trastuzumab started concomitantly with docetaxel (AC→TH) (n = 1,074).
- Experimental treatment of six cycles of docetaxel 75 mg/m2 and carboplatin to AUC 6 with 1 year of trastuzumab, the latter started at the same time as the chemotherapy (TCH) (n = 1,074).