Randomized Phase II Trial of Weekly vs. Every 2 Weeks vs. Every 3 Weeks Nanoparticle Albumin-Bound Paclitaxel With Bevacizumab as First-Line Chemotherapy for Metastatic Breast Cancer

This randomized phase II trial tested nanoparticle albumin-bound paclitaxel (nab-P) in 3 different schedules: weekly, every 2 weeks (q2W), and every 3 weeks (q3W). Because bevacizumab prolonged progression-free survival in earlier trials with taxanes in metastatic breast cancer (MBC), all the patients received this agent. Weekly nanoparticle albumin-bound paclitaxel (nab-P) appeared to have the highest therapeutic index, but treatment was limited by sensory neuropathy. Background: Nanoparticle albumin-bound paclitaxel (nab-P) and bevacizumab have each demonstrated efficacy in patients with MBC. This trial was designed to further develop nab-P by evaluating its efficacy and safety using every 3 weeks (q3w), every 2 weeks (q2w), or weekly scheduling in combination with bevacizumab as first-line treatment of MBC. Patients and Methods: This open-label phase II study randomized patients to nab-P 260 mg/m(2) q3w (arm A) vs. 260 mg/m(2) q2w with filgrastim (arm B) vs. 130 mg/m(2) weekly uninterrupted, all with bevacizumab (15 mg/kg q3w arm A, 10 mg/kg q2w arms B and C). The primary endpoints were overall response rate (ORR) and toxicity. Time to tumor progression (TTP) and overall survival were secondary endpoints. Results: Of 212 patients randomized, 208 (arm A, 75; arm B, 54; arm C, 79) were treated. Arm B was closed early due to toxicity, with more grade >= 2 fatigue (arm A, 46%; arm B, 62%; arm C, 62%) and bone pain (arm A, 11%; arm B, 23%; arm C, 5%). Neurotoxicity grade >= 2 was equivalent across the arms (> 50%) and reversible for most patients. Febrile neutropenia occurred in <= 3% of patients in all arms. ORR was similar among the arms (arm A, 45%; arm B, 41%; arm C, 46%). Median TTP was slightly longer in arm C (9.0 months) vs. arms A (8.0 months) and B (5.8 months) (overall, P = .105). Conclusions: Significant antitumor activity was observed in all the arms. Weekly nab-P with bevacizumab appeared to have the highest therapeutic index. However, sensory neuropathy was treatment limiting, which suggests that a 3 weeks on and 1 week off schedule should be explored.