Multicenter Randomized Open-Label Phase II Clinical Study Comparing Outcomes of NK105 and Paclitaxel in Advanced or Recurrent Breast Cancer

Background: NK105 is a paclitaxel (PTX)-incorporating "core-shell-type" polymeric micellar nanoparticle formulation composed block copolymers (polyethylene glycol and a polyamino acid). The efficacy and safety of NK105 and paclitaxel in advanced recurrent breast cancer have never been compared at equivalent dose levels. Patients and Methods: Patients were randomly assigned to either NK105 or PTX in a 1:1 ratio. The study drug was administered on Day 1, 8, and 15 of a 28-day cycle with 80 mg/m2. The primary endpoint was overall response rate (ORR), secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events. Results: A total of 123 patients (NK105, n=62; PTX, n=61) received one of the two drugs. There was no significant difference ORR, the median PFS, or OS (NK105 group: 41.9%, 9.1, and 27.5 months, respectively; PTX group: 45.9%, 7.8, and 32.4 months, respectively). Neutropenia occurred more frequently in the NK105 group, but most patients did not require granulocyte-colony stimulating factor or dose-reduction. The median time to onset of peripheral sensory neuropathy (PSN) in the NK105 group was significantly longer than that in the PTX group (p=0.001), and PSN (>= grade 3) was not observed in the NK105 group. Conclusion: Weekly NK105 administration was well-tolerated. Efficacy was similar in both groups. The PSN profile was better in the NK105 group. Keywords: polymeric micellar nanoparticles, chemotherapy-induced peripheral neuropathy, taxane, anti-polyethylene glycol overall rate