Paclitaxel (PTX) is a standard chemotherapy drug for metastatic or recurrent breast cancer (m/r BC). However, it presents problems such as hypersensitivity and peripheral sensory neuropathy (PSN). NK105 is a novel nanoparticle drug delivery formulation that encapsulates PTX in polymeric micelles. In a murine model, passive targeting was shown and NK105 accumulated in tumors. We expected NK105 to have similar efficacy and a better safety profile, regarding hypersensitivity and PSN, compared with PTX, considering a past phase II study in gastric cancer patients (pts). This study aimed to verify the non-inferiority of NK105 to PTX in terms of progression-free survival (PFS) in m/r BC pts.
Eligible pts were randomly assigned at a 1:1 ratio to either the NK105 (N) or PTX (P) arm. NK105 (65 mg/m2) and PTX (80 mg/m2) were administered via intravenous infusion weekly for 3 weeks followed by a 1-week rest period until disease progression. Tumor responses were assessed every 6 weeks by RECIST Ver. 1.1. The primary endpoint was PFS, while the secondary endpoints were overall response rate (ORR), overall survival (OS), and safety. PSN was evaluated by CTCAE Ver. 4.03 and FACT/GOG-NTX Ver. 4 (FACT).
From September 2012 to July 2014, 436 pts were randomized and 422 pts were included in the efficacy analysis. The median PFS (95% CI) for the N and P arms was 256 (212–302) and 260 days (211–350), respectively. The adjusted hazard ratio (95% CI) was 1.255 (0.989–1.592), exceeding the set non-inferiority margin. The ORR and median OS for the N and P arms were 31.6% vs. 39.0%, and 950 vs. 1103 days, respectively. Adverse drug reactions occurred in 96.7% pts in the N arm and 98.1% in the P arm. PSN incidences in the N and P arms were 52.8% and 70.0%, respectively and incidence of Grade 3 or more was lower in the N arm than in the P arm pts. Cumulative PSN incidences between the N and P arms were significantly different (P
The efficacy of 65 mg/m2 of NK105 could not be verified in terms of non-inferiority of PFS relative to PTX in this study. NK105 safety profile was generally similar to that of PTX, but the NK105 PSN profile was better than that of PTX. NK105 efficacy should be re-evaluated in future studies.
Clinical trial identification
Legal entity responsible for the study
Nippon Kayaku Co., Ltd.
Nippon Kayaku Co., Ltd.
Y. Tokuda: Obtained financial support for research activity from Nippon Kayaku Co., Ltd. in 2014, 2015, and 2016. Y. Nambu: Managing Director and Head of Pharmaceuticals Group of Nippon Kayaku Co., Ltd. All other authors have declared no conflicts of interest.