250P - A Global Phase III Clinical Study Comparing NK105 and Paclitaxel in Metastatic or Recurrent Breast Cancer Patients

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Clinical research
Breast Cancer
Basic Scientific Principles
Biological therapy
Presenter Toshiaki Saeki
Citation Annals of Oncology (2017) 28 (suppl_5): v74-v108. 10.1093/annonc/mdx365
Authors T. Saeki1, H. Mukai2, J. Ro3, Y. Lin4, Y. Fujiwara5, S. Nagai6, K.S. Lee7, J. Watanabe8, S. Ohtani9, S. Kim10, K. Kuroi11, K. Tsugawa12, Y. Tokuda13, H. Iwata14, Y.H. Park15, Y. Yang16, Y. Nambu17
  • 1Department Of Breast Oncology, Saitama Medical University International Medical Center, 3501298 - Saitama/JP
  • 2Breast And Medical Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 3Graduate School Of Cancer Science And Policy, National Cancer Center, 410-769 - Goyang/KR
  • 4Division Of Haematology And Oncology, Chang-Gung Memorial Hospital, Linko, Taoyuan/TW
  • 5Department Of Breast And Medical Oncology, National Cancer Center Hospital, Tokyo/JP
  • 6Division Of Breast Oncology, Saitama Cancer Center, Saitama/JP
  • 7Center For Breast Cancer, National Cancer Center, Seoul/KR
  • 8Breast Oncology, Shizuoka Cancer Center, Shizuoka/JP
  • 9Department Of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, 730-0011 - Hiroshima/JP
  • 10Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 11Department Of Surgery, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo/JP
  • 12Division Of Breast And Endocrine Surgery, Department Of Surgery, St. Marianna University School of Medicine, Kawasaki/JP
  • 13Department Of Breast And Endocrine Surgery, Tokai University School of Medicine, 259-1193 - Isehara/JP
  • 14Department Of Breast Oncology, Aichi Cancer Center Hospital, Nagoya/JP
  • 15Division Of Hematology-oncology, Samsung Medical Center, Seoul/KR
  • 16Department Of Hematology-oncology, Taichung Veterans General Hospital, Taichung/TW
  • 17Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo/JP



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.