A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study): primary analysis

Hisashi Tanaka; Shigeru Tanzawa; Toshihiro Misumi; Tomonori Makiguchi; Megumi Inaba; Takeshi Honda; Junya Nakamura; Koji Inoue; Takayuki Kishikawa; Masanao Nakashima; Keiichi Fujiwara; Tadashi Kohyama; Hiroo Ishida; Shoichi Kuyama; Naoki Miyazawa; Tomomi Nakamura; Hiroshi Miyawaki; Naohiro Oda; Nobuhisa Ishikawa; Ryotaro Morinaga; Kei Kusaka; Nobukazu Fujimoto; Yasushi Fukuda; Masayuki Yasugi; Takeshi Tsuda; Sunao Ushijima; Kazuhiko Shibata; Takuo Shibayama; Akihiro Bessho; Kyoichi Kaira; Kenshiro Shiraishi; Noriyuki Matsutani; Nobuhiko Seki

doi:10.1177/17588359221142786

A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study): primary analysis

Ther Adv Med Oncol. 2022 Dec 18:14:17588359221142786. doi: 10.1177/17588359221142786. eCollection 2022.

Authors

Hisashi Tanaka¹, Shigeru Tanzawa², Toshihiro Misumi³, Tomonori Makiguchi¹, Megumi Inaba⁴, Takeshi Honda², Junya Nakamura⁵, Koji Inoue⁵, Takayuki Kishikawa⁶, Masanao Nakashima⁷, Keiichi Fujiwara⁸, Tadashi Kohyama⁹, Hiroo Ishida¹⁰, Shoichi Kuyama¹¹, Naoki Miyazawa¹², Tomomi Nakamura¹³, Hiroshi Miyawaki¹⁴, Naohiro Oda¹⁵, Nobuhisa Ishikawa¹⁶, Ryotaro Morinaga¹⁷, Kei Kusaka¹⁸, Nobukazu Fujimoto¹⁹, Yasushi Fukuda²⁰, Masayuki Yasugi²¹, Takeshi Tsuda²², Sunao Ushijima²³, Kazuhiko Shibata²⁴, Takuo Shibayama⁸, Akihiro Bessho²⁵, Kyoichi Kaira²⁶, Kenshiro Shiraishi²⁷, Noriyuki Matsutani²⁸, Nobuhiko Seki²⁹

Affiliations

¹ Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
² Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.
³ Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
⁴ Department of Respiratory Medicine, Kumamoto Chuo Hospital, Kumamoto, Kumamoto, Japan.
⁵ Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan.
⁶ Department of Respiratory Medicine, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan.
⁷ Department of Respiratory Medicine, Shin-Yurigaoka General Hospital, Kawasaki, Kanagawa, Japan.
⁸ Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Okayama, Japan.
⁹ Department of Internal Medicine, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, Japan.
¹⁰ Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan.
¹¹ Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan.
¹² Department of Respiratory Medicine, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Kanagawa, Japan.
¹³ Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Saga, Japan.
¹⁴ Department of Respiratory Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan.
¹⁵ Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Hiroshima, Japan.
¹⁶ Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Hiroshima, Japan.
¹⁷ Department of Thoracic Medical Oncology, Oita Prefectural Hospital, Oita, Oita, Japan.
¹⁸ The Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, Kiyose, Tokyo, Japan.
¹⁹ Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Okayama, Japan.
²⁰ Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Okayama, Japan.
²¹ Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima, Japan.
²² Department of Respiratory Medicine, Toyama Prefectural Central Hospital, Toyama, Toyama, Japan.
²³ Department of Medical Oncology, Kumamoto Kenhoku Hospital, Tamana, Kumamoto, Japan.
²⁴ Department of Medical Oncology, Kouseiren Takaoka Hospital, Takaoka, Toyama, Japan.
²⁵ Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Okayama, Japan.
²⁶ Department of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
²⁷ Department of Radiology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.
²⁸ Department of Surgery, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, Japan.
²⁹ Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.

Abstract

Background: The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported.

Objectives: We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy. Here, we report the primary analysis results.

Design: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m², day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab (10 mg/kg) every 2 weeks for up to 1 year.

Methods: The primary endpoint was 1-year progression-free survival (PFS). The expected 1-year PFS and its lower limit of the 80% confidence interval (CI) were set as 63% and 47%, respectively, based on the results of TORG1018 study.

Results: In all, 59 patients were enrolled, with 51 (86.4%) proceeding to durvalumab. The objective response rate throughout the study was 72.9% (95% CI: 59.7-83.6%). After median follow-up of 21.9 months, neither median PFS nor OS was reached. The 1-year PFS was 72.5% (80% CI: 64.2-79.2%, 95% CI: 59.1-82.2%), while the 1-year overall survival was 91.5% (95% CI: 80.8-96.4%). No grade 5 adverse events were observed throughout the study. The most common adverse event during the consolidation phase was pneumonitis (any grade, 78.4%; grade ⩾3, 2.0%). Eventually, 52.5% of patients completed 1-year durvalumab consolidation therapy from CRT initiation.

Conclusion: This study of durvalumab after SP-based CRT met its primary endpoint and found a 1-year PFS of 73% from CRT initiation. This study provides the first prospective data on the prognosis and tolerability of durvalumab consolidation from the initiation of CRT.

Trial registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

Keywords: S-1; chemoradiotherapy; cisplatin; durvalumab; non-small-cell lung cancer.