Randomized phase III trial of trastuzumab monotherapy followed by trastuzumab plus docetaxel versus trastuzumab plus docetaxel as first-line therapy in patients with HER2-positive metastatic breast cancer: the JO17360 Trial Group

Abstract

We evaluated the efficacy and safety of sequential therapy with trastuzumab monotherapy (H-mono) followed by H plus docetaxel (D) after disease progression (H → H + D) versus combination therapy with H + D as first-line therapy. Patients with human epidermal growth factor receptor type 2 (HER2)-positive metastatic breast cancer (MBC) and left ventricular ejection fraction >50% were randomly assigned to either (a) H → H + D [H, once weekly 2 mg/kg (loading dose, 4 mg/kg); D, once every 3 weeks 60 mg/m²] or (b) H + D. Primary endpoints were progression-free survival (PFS) for the H-mono stage of the H → H + D group and H + D group and overall survival (OS) for both groups. Secondary endpoints were overall response rate, time to treatment failure, second PFS and safety. The planned number of patients was 160 patients in total. Of 112 patients enrolled, 107 were eligible. After 112 patients were enrolled, the Independent Data Monitoring Committee recommended stopping enrollment because PFS and OS were greater in the H + D group than the H → H + D group. Median PFS was 445 days in the H + D group versus 114 days for H-mono in the H → H + D group [hazard ratio (HR), 4.24; P < 0.01]. OS was significantly longer in the H + D group (HR, 2.72; P = 0.04). H + D therapy is significantly superior to H → H + D therapy as first-line therapy in patients with HER2-positive MBC, especially in terms of OS.

Appendix

Contributions

Conception and design: Yasuo Ohashi, Masashi Ando, Toru Watanabe.

Financial support: Chugai Pharmaceutical Co., Ltd.

The following investigators and institutions also participated in the trial:

Junichiro Watanabe, Shizuoka Cancer Center, Shizuoka, Japan; Yoshinori Ito, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; Keisei Anan, Kitakyushu Municipal Medical Center, Fukuoka, Japan; Yuichi Takatsuka, Kansai Rosai Hospital, Hyogo, Japan; Hitoshi Arioka, Yokohama Rosai Hospital, Kanagawa, Japan; Kenichi Watanabe, Hokkaido Cancer Center, Hokkaido, Japan; Reiki Nishimura, Kumamoto Municipal Hospital, Kumamoto, Japan; Kenjiro Aogi, National Hospital Organization Shikoku Cancer Center, Ehime, Japan; Seigo Nakamura, St. Luke’s International Hospital, Tokyo, Japan; Nobuaki Sato, Niigata Cancer Center Hospital, Niigata, Japan; Masato Koseki, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan; Yutaka Tokuda, Tokai University Hospital, Kanagawa, Japan; Shinji Ohno, National Kyushu Cancer Center, Fukuoka, Japan; Shigeru Murakami, Hiroshima University Hospital, Hiroshima, Japan; Akihiko Chiba, Kanagawa Cancer Center, Kanagawa, Japan; Hideo Inaji, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Shintaro Takao, Hyogo Cancer Center, Hyogo, Japan; Hiroko Yamashita, Nagoya City University Hospital, Aichi, Japan; Syouji Oura. Wakayama Medical University Hospital, Wakayama, Japan.

Data analysis and interpretation: Yasuo Ohashi, Shigeto Miura, Kenji Eguchi, Tetsu Shinkai.

Manuscript writing: Kenichi Inoue, Kazuhiko Nakagami, Mitsuhiro Mizutani, Yasuo Hozumi, Yasuhiro Fujiwara, Norikazu Masuda, Fumine Tsukamoto, Mitsue Saito, Shigeto Miura, Kenji Eguchi, Tetsu Shinkai, Masashi Ando, Toru Watanabe, Noriyuki Masuda, Yasuo Ohashi, Muneaki Sano, Shinzaburo Noguchi. Editorial assistance was provided by Medi-Kelsey Limited. All authors contributed materially to drafts and revisions and approved the final manuscript.

Final approval of manuscript: Kenichi Inoue, Yasuo Ohashi, Shinzaburo Noguchi.