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

Abstract 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.