학술논문
Multicenter Randomized Open-Label Phase II Clinical Study Comparing Outcomes of NK105 and Paclitaxel in Advanced or Recurrent Breast Cancer
Document Type
article
Author
Source
International Journal of Nanomedicine, Vol Volume 17, Pp 4567-4578 (2022)
Subject
Language
English
ISSN
1178-2013
Abstract
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