Phase II Trial of Gemcitabine/Carboplatin (plus Trastuzumab in HER2-Positive Disease) in Patients with Metastatic Breast Cancer

BackgroundGemcitabine and carboplatin have significant preclinical synergy, and both provide synergistic antitumor activity in metastatic breast cancer (MBC) when used in combination with trastuzumab. The gemcitabine/cisplatin combination is highly active in MBC with response rates (RRs) of approximately 50% in anthracycline-and taxane-pretreated patients and up to 80% in untreated subjects. This phase II trial studied the efficacy and safety of gemcitabine/carboplatin with or without trastuzumab in patients with MBC.Patients and MethodsPatients were stratified into 3 groups: group 1, HER2-positive; group 2, HER2-negative and taxane-naive/remote (no taxanes within past 2 years); and group 3, HER2-negative and previous taxane therapy. Included were women aged ≥ 18 years, Eastern Cooperative Oncology Group performance status of 0-2, with Response Evaluation Criteria in Solid Tumors–defined measurable MBC; HER2-negative or HER2 (3+) by immunohistochemistry or fluorescence in situ hybridization positive. All cycles were repeated every 14 days. On day 1, gemcitabine 1500 mg/m2 over 30 minutes was administered followed by carboplatin area under the curve of 2.5. Group 1 also received trastuzumab 8 mg/kg on day 1 of each cycle followed by 4 mg/kg for every 2 weeks thereafter.ResultsOne hundred fifty patients were registered (50, 51, and 49 in groups 1, 2, and 3, respectively). The overall RRs were 64%, 27%, and 32%, respectively, with median time to progression of 7.2, 5.5, and 4.4 months, respectively. Overall, grade 3/4 toxicities included neutropenia (45%), leukopenia (17%), and thrombocytopenia (7%). Alopecia was infrequent: grade 1 (34%) and grade 2 (3%), and there was no significant cardiac toxicity.ConclusionGemcitabine/carboplatin/trastuzumab is highly active in patients with HER2-positive MBC. Gemcitabine/carboplatin is active in patients with HER2-negative MBC independent of previous taxane therapy. Gemcitabine/carboplatin with or without trastuzumab administered every 2 weeks is associated with a low frequency of serious toxicity.