In the first overall survival analysis of the BCIRG 007 study in metastatic breast cancer, the addition of carboplatin to a docetaxel (Taxotere)/trastuzumab (Herceptin) regimen did not improve overall survival.
ASCOIn the first overall survival analysis of the BCIRG 007 study in metastatic breast cancer, the addition of carboplatin to a docetaxel (Taxotere)/trastuzumab (Herceptin) regimen did not improve overall survival. Mark Pegram, MD, of the UCLA David Geffen School of Medicine, reported the results at the 2007 American Society of Clinical Oncology annual meeting (abstract LBA1008).
"There was no enhanced efficacy for the addition of carboplatin to trastuzumab plus docetaxel. Both regimens were effective, but there were differences in toxicities," Dr. Pegram reported.
The 007 study of the Breast Cancer International Research Group (BCIRG) is a phase III trial in HER2-positive metastatic breast cancer patients previously untreated for metastatic disease. A total of 263 patients were randomized to receive one of the following regimens:
• Docetaxel, 100 mg/m2 every 3 weeks for eight cycles, plus trastuzumab,
2 mg/kg loading, followed by 6 mg/kg every 3 weeks for 1 year (TH).
• Docetaxel 75 mg/m2 plus carboplatin to AUC 6 every 3 weeks for eight cycles plus trastuzumab (TCH).
No significant differences were observed between TH and TCH with regard to median time to progression (11.1 vs 10.4 months, respectively) and overall response rate (73% in each arm). At a median follow-up of 39 months, median overall survival was 36.4 and 36.6 months, respectively, Dr. Pegram reported.
Among grade 3-4 hematologic toxicities, febrile neutropenia rates were similar for TH and TCH. There was a trend toward more neutropenic infections with TH, but there were no septic deaths in the TH arm vs two in the TCH arm, "a cautionary note," he said. There was significantly more thrombocytopenia in the TCH arm (15% vs 2% for TH), but Dr. Pegram noted that none of the thrombocytopenia events were associated with bleeding symptoms or platelet transfusion.
Nonhematologic toxicities were rare, though significant differences were observed per arm. There was a significantly greater incidence of sensory neuropathy, myalgia, and skin and nail toxicity with TH and significantly more nausea and vomiting with TCH.
"Just one patient had a grade 3 left ventricular dysfunction in the TH arm," Dr. Pegram said. "Otherwise, there were no meaningful differences between the two regimens with regard to cardiac safety."
More Cycles With TCH
Women on the TCH arm received more cycles of chemotherapy (79% completed eight cycles vs 64% on TH) and were less likely to discontinue treatment as a result of nonhematologic toxicity.
Dr. Pegram added that, contrary to a conclusion from an initial faulty statistical analysis, reported at ASCO 2006, the carboplatin dose intensity was not low but was 97.4%. The relative dose intensities of the regimens, therefore, were similar, "so this cannot explain any lack of efficacy in the TCH arm," he said.
Dr. Pegram also commented that since the docetaxel dose varied between the arms, some contribution of carboplatin, "however limited," in the TCH arm cannot be ruled out.
Session moderator Clifford Hudis, MD, chief of the Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, commented: "This is an elegant demonstration of real equivalency of regimens in the metastatic setting. This speaks to the need to pursue TCH in the adjuvant approach. One could argue that TCH may still get the nod in terms of feasibility in delivering the planned number of cycles."
Discussant Luca Gianni, MD, of the Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, agreed. "Survival data are identical between TCH and TH; therefore, tolerability is what is left, in terms of deciding between the two regimens," he said.
He cited more infections and neutropenic infections with TH and more thrombocytopenia and diarrhea with TCH, but highlighted the "clinically relevant toxicities" as increased sensory and motor neuropathy, myalgia, and skin and nail toxicity with TH. "You make your pick based on this because activity is the same," he said.
Dr. Gianni also noted that since trastuzumab was discontinued after 52 weeks in this study, "it makes you wonder about the possibility of further improving outcomes with longer treatment."
Take Home Point
• Trastuzumab (Herceptin)/docetaxel (Taxotere) (TH) had equal efficacy to a TCH regimen (carboplatin added and docetaxel dose reduced).
• Toxicity profiles differed with more neuropathy, myalgia, and skin toxicity with TH, and more thrombocytopenia, nausea, vomiting, and diarrhea with TCH.