Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment

Purpose The objective of this phase III global study was to compare the efficacy of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced breast cancer. It was designed as a pivotal study for the approval of G for a breast cancer treatment indication. Patients and Methods Patients who relapsed after adjuvant anthracyclines were randomly assigned to gemcitabine, 1,250 mg/m(2) days 1 and 8 plus paclitaxel, 175 mg/m2 on day 1; or, to paclitaxel at same dose on day 1 (both arms administered every 21 days, unblinded). The primary end point was overall survival ( OS) and secondary end points were time to progression (TTP), response rate (RR), progression-free survival, response duration, and toxicity. This final OS analysis was planned at 380 deaths. Results A total of 266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489), with an adjusted Cox hazard ratio of 0.78 (95% Cl, 0.64 to 0.96; P = .0187). The TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT. Conclusion This phase III study documents a role for gemcitabine in advanced breast cancer after anthracycline-based adjuvant therapy. The results establish GT as a reasonable choice for women who require cytoreduction with manageable toxicities and validate ongoing testing of GT in the adjuvant setting.