SAN ANTONIOThe three-drug combination of carboplatin(Drug information on carboplatin) (Paraplatin), paclitaxel(Drug information on paclitaxel) (Taxol), and trastuzumab(Drug information on trastuzumab) (Herceptin) increases response rate and time to progression among HER-2-positive patients with advanced breast cancer, compared with the trastuzumab/paclitaxel combination alone, according to Nicholas J. Robert, MD, chairman of research at Inova Fairfax Hospital’s Cancer Center, Fairfax, Virginia, and co-chairman of the Breast Committee of the US Oncology Research Network.
Speaking at the 25th Annual San Antonio Breast Cancer Symposium (abstract 35), Dr. Robert noted that the improvements in efficacy were accompanied by moderate, but acceptable, increases in toxicity.
As background, Dr. Robert reviewed the results of the pivotal trial that established the superiority of trastuzumab and paclitaxel (TP) over paclitaxel alone. In that trial, the TP combination produced a response rate of 41% vs 17% for pac-litaxel alone. Time to progression increased from 3.0 months on the single-agent therapy to 6.9 months on the combination.
Looking for a regimen to improve upon these results, the researchers considered the documented activity of carboplatin and taxanes. In three phase II trials of first-line paclitaxel and carboplatin in breast cancer patients, Dr. Robert noted, the combination produced response rates ranging from 53% to 62%.
"These response rates are competitive with those of anthracycline-containing regimens, and we know that anthracy-cline-containing regimens are active with trastuzumab," he said. "But we’re also concerned about the increased cardiotox-icity of greater than 25%. With this approach, we hoped to find a regimen where we could avoid the anthracycline/trastuzumab cardiotoxicity."
The current phase III trial was designed to evaluate response rate, time to progression, survival, and toxicity among stage IV, HER-2-positive breast cancer patients receiving trastuzumab, pacli-taxel, and carboplatin (TPC) vs TP alone.
The trial enrolled 196 patients who were designated HER-2 2+ or 3+ by immunohistochemistry (IHC) (Hercep-Test) in a central laboratory. The trial was later amended so that 2+ patients had to be positive on fluorescent in situ hybridization (FISH) to be eligible. Patients had received no prior chemotherapy for metastatic disease and had an ECOG performance status of 0 to 2.