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Neoadjuvant carboplatin induced responses in triple-negative breast cancer
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Neoadjuvant carboplatin added to a taxane, anthracycline and targeted therapy improved the response rate among women with triple-negative breast cancer, but not among those with HER-2–positive breast cancer, according to phase 2 study results.
Gunter von Minckwitz, MD, of the German Breast Group in Neu-Isenburg, Germany, and colleagues evaluated data from 315 women with triple-negative breast cancer and 273 women with HER-2–positive breast cancer. All women were previously untreated and had non-metastatic, stage II to stage III disease.
Study participants received 80 mg/m2 paclitaxel and 20 mg/m2 non-pegylated liposomal doxorubicin weekly for 18 weeks. Patients with triple-negative breast cancer also received 15 mg/kg bevacizumab (Avastin, Genentech) every 3 weeks, whereas patients with HER-2–positive breast cancer received an 8-mg/kg loading dose of trastuzumab (Herceptin, Genentech) followed by 6-mg/kg doses every 3 weeks plus 750 mg daily lapatinib (Tykerb, GlaxoSmithKline).
Researchers then assigned 295 patients to also receive carboplatin concurrently with the backbone regimen. The other 293 patients received no carboplatin.
A higher percentage of patients assigned carboplatin achieved a pathological complete response (43.7% vs. 36.9%); however, this difference was not statistically significant (OR=1.33; 95% CI, 0.96-1.85).
Researchers then stratified analyses according to disease type. Among patients with triple-negative breast cancer, a significantly higher percentage of patients assigned carboplatin achieved a complete response (53.2% vs. 36.9%; P=.005).
However, complete response rates were comparable among patients with HER-2–positive disease who did and did not receive carboplatin (32.8% vs. 36.8%; P=.581).
Significantly higher rates of patients assigned carboplatin experienced grade 3 or grade 4 neutropenia (65% vs. 27%), anemia (15% vs. ˂1%), thrombocytopenia (14% vs. ˂1%) and diarrhea (17% vs. 11%). Treatment discontinuation occurred more frequently in the carboplatin arm (48% vs. 39%; P=.031).
When researchers reduced carboplatin doses from area under the curve 2.0 to 1.5, they observed a reduction in grade 3 and grade 4 hematological (82% to 70%) and non-hematological (78% to 59%) events.
“The addition of neoadjuvant carboplatin to a regimen of a taxane, an anthracycline and targeted therapy significantly increases the proportion of patients achieving a pathological complete response,” the researchers concluded. “This regimen seems to increase responses in patients with triple-negative breast cancer, but not in those with HER-2–positive breast cancer.”
Disclosure: The study was funded by GlaxoSmithKline, Roche and Teva.
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