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

Yoshimasa Kosaka,1– 3 Toshiaki Saeki,2 Toshimi Takano,4,5 Tomoyuki Aruga,6 Toshinari Yamashita,7 Norikazu Masuda,8,9 Yukio Koibuchi,10 Akihiko Osaki,2 Junichiro Watanabe,11,12 Ryu Suzuki13 1Department of Breast and Endocrine Surgery, Kitasato University School of Medicine, Sagamihara-shi, Kanagawa, Japan; 2Department of Breast Oncology, Saitama Medical University International Medical Center, Hidaka-shi, Saitama, Japan; 3Department of Breast Oncology, Japanese Red Cross Sagamihara Hospital, Sagamihara-shi, Kanagawa, Japan; 4Department of Medical Oncology, Toranomon Hospital, Minato-ku, Tokyo, Japan; 5Breast Medical Oncology Department, Breast Oncology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan; 6Department of Breast Surgery, Tokyo Metropolitan Center and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan; 7Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama-shi, Kanagawa, Japan; 8Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka-shi, Osaka, Japan; 9Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya-shi, Aichi, Japan; 10Department of Breast and Endocrine Surgery, National Hospital Organization Takasaki General Medical Center, Takasaki-shi, Gunma, Japan; 11Division of Breast Oncology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan; 12Department of Breast Oncology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan; 13Pharmaceuticals Group, Nippon Kayaku Co., Ltd, Kita-ku, Tokyo, JapanCorrespondence: Yoshimasa Kosaka, Department of Breast Oncology, Japanese Red Cross Sagamihara Hospital, 256 Nakano, Midori-ku, Sagamihara-shi, Kanagawa, 252-0157, Japan, Tel +81-42-784-1101, Email y-kosaka@med.kitasato-u.ac.jpBackground: NK105 is a paclitaxel (PTX)-incorporating “core-shell-type” polymeric micellar nanoparticle formulation composed of block copolymers (polyethylene glycol and a polyamino acid). The efficacy and safety of NK105 and paclitaxel in advanced or 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 in 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 antibodies, overall response rate