Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial.

BACKGROUND: We aimed to compare the additional benefit of gemcitabine when combined with vinorelbine above that of standard vinorelbine treatment in patients with metastatic breast cancer. METHODS: In this phase III, multicentre, open-label, randomised study, 252 women with locally recurrent and metastatic breast cancer who had been pretreated with anthracyclines and taxanes were randomly assigned single-agent vinorelbine (30 mg/m(2), days 1 and 8) or gemcitabine plus vinorelbine (1200/30 mg/m(2), days 1 and 8). Both study treatments were administered intravenously every 21 days until disease progression, unacceptable toxic effects, or stoppage at the request of investigator or patient. The primary endpoint was median progression-free survival. Secondary objectives included assessments of response rate, disease duration, overall survival, and characterisation of the toxicity profiles of both regimens. This study is registered with ClinicalTrials.gov, number NCT00128310. FINDINGS: Between 2001 and 2005, 252 women were recruited and randomised for treatment. One of these patients was ineligible. Prognostic factors were well balanced between treatment groups (median number of metastatic sites in combination group 2 (range 0-5) and in vinorelbine group 2 (range 1-6); visceral disease in 76% and 75% of patients, respectively). Median progression-free survival was 6.0 months (95% CI 4.8-7.1) for patients given gemcitabine plus vinorelbine and 4.0 months (2.9-5.1) for those assigned vinorelbine; there was 1.9 months of difference (hazard ratio 0.66 [0.50-0.88]; p=0.0028). Overall survival was 15.9 months (12.6-19.1) for the gemcitabine plus vinorelbine group and 16.4 months (11.6-21.0) for the vinorelbine group; there was 0.5 months of difference (hazard ratio 1.04 [0.78-1.39]; p=0.8046). Objective response rates were 36% for patients assigned gemcitabine plus vinorelbine (n=45) and 26% for those assigned vinorelbine (n=33) (p=0.093). Grade 3 or 4 neutropenia was reported in 75 (61% [52-70]) of the participants assigned gemcitabine plus vinorelbine, compared with 55 (44% [35-53]) of those assigned vinorelbine alone (p=0.0074). Febrile neutropenia occurred in 13 (11%) of those assigned gemcitabine plus vinorelbine, and in seven (6%) of those assigned vinorelbine alone (p=0.15). Incidences of grade 3 or 4 non-haematological toxic effects were similar between the two treatment groups. INTERPRETATION: Patients with metastatic breast cancer assigned gemcitabine and vinorelbine had better progression-free survival compared with those assigned vinorelbine alone. However, this finding did not translate into a difference in overall survival. Although toxicity was manageable, patients in the combined group had more haematological toxic effects. These factors should be taken into account when deciding which chemotherapy patients should receive.