A randomized phase II study evaluating different maintenance schedules of nab-Paclitaxel in the first-line treatment of metastatic breast cancer: final results of the IBCSG 42-12/BIG 2-12 SNAP trial.

Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: Arm A, nab-Paclitaxel 150 mg/m2 days 1,15 Q28; Arm B, nab-Paclitaxel 100 mg/m2 days 1,8,15 Q28; Arm C, nab-Paclitaxel 75 mg/m2 days 1,8,15,22 Q28. Induction was three cycles nab-Paclitaxel 150/125 mg/m2, days 1,8,15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared to the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life evaluation was performed, global indicator for physical well-being was defined as the primary endpoint; completion rates of quality-of-life forms were >90%. Results: 255 patients were evaluable for the primary endpoint. After 18.2 months median follow-up, 182 PFS events were observed. Median PFS was 7.9 months (90%CI 6.8-8.4) in Arm A, 9.0 months (90%CI 8.1-10.9) in Arm B and 8.5 months (90%CI 6.7-9.5) in Arm C. PFS in Arm B was significantly longer than the historical reference of first-line docetaxel (P=0.03). Grade>/=2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of patients in Arm A, Arm B and Arm C, respectively (Grade>/=3 in 9.1%, 5.6% and 6.6% of patients, respectively). Noteworthy, the quality-of-life scores for sensory neuropathy did not worsen with prolonged nab-Paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-Paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225.