Akihito Kawazoe1, Kensei Yamaguchi2, Hisateru Yasui3, Yuji Negoro4, Mizutomo Azuma5, Kenji Amagai6, Hiroki Hara7, Hideo Baba8, Masahiro Tsuda9, Hisashi Hosaka10, Hisato Kawakami11, Takashi Oshima12, Yasushi Omuro13, Nozomu Machida14, Taito Esaki15, Kazuhiro Yoshida16, Tomohiro Nishina17, Yoshito Komatsu18, Shi R Han19, Shinichi Shiratori20, Kohei Shitara21. 1. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: akawazoe@east.ncc.go.jp. 2. Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: kensei.yamaguchi@jfcr.or.jp. 3. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan. Electronic address: hyasui@kcho.jp. 4. Department of Gastroenterology, Kochi Health Sciences Center, Kochi, Japan. Electronic address: tp-negoro@mx1.tiki.ne.jp. 5. Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan. Electronic address: mizutomo@med.kitasato-u.ac.jp. 6. Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan. Electronic address: k-amagai@chubyoin.pref.ibaraki.jp. 7. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. Electronic address: hirhara@cancer-c.pref.saitama.jp. 8. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: hdobaba@kumamoto-u.ac.jp. 9. Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi, Japan. Electronic address: ma.tsuda@hyogo-cc.jp. 10. Department of Gastroenterology, Gunma Prefectural Cancer Center, Gunma, Japan. Electronic address: hosaka@gunma-cc.jp. 11. Department of Medical Oncology, Kindai University Faculty of Medicine, Osakasayama, Japan. Electronic address: kawakami_h@med.kindai.ac.jp. 12. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan. Electronic address: oshimat@kcch.jp. 13. Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. Electronic address: yomuro@cick.jp. 14. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. Electronic address: no.machida@scchr.jp. 15. Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. Electronic address: esaki.taito.fz@mail.hosp.go.jp. 16. Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan. Electronic address: kyoshida@gifu-u.ac.jp. 17. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. Electronic address: nishina.tomohiro.nj@mail.hosp.go.jp. 18. Division of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan. Electronic address: ykomatsu@ac.cyberhome.ne.jp. 19. MSD K.K., Tokyo, Japan. Electronic address: shi.rong.han@merck.com. 20. MSD K.K., Tokyo, Japan. Electronic address: shinichi.shiratori@merck.com. 21. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: kshitara@east.ncc.go.jp.
Abstract
AIM: The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab). METHODS: This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status. RESULTS: Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%). CONCLUSIONS: SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer. TRIAL REGISTRATION: NCT03382600/JapicCTI-183829.
AIM: The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab). METHODS: This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, humanepidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status. RESULTS: Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%). CONCLUSIONS: SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer. TRIAL REGISTRATION: NCT03382600/JapicCTI-183829.
Authors: Vivien Koh; Jayati Chakrabarti; Meaghan Torvund; Nina Steele; Jennifer A Hawkins; Yoshiaki Ito; Jiang Wang; Michael A Helmrath; Juanita L Merchant; Syed A Ahmed; Asim Shabbir; Jimmy Bok Yan So; Wei Peng Yong; Yana Zavros Journal: Cancer Lett Date: 2021-06-12 Impact factor: 8.679
Authors: M Pötzsch; E Berg; M Hummel; U Stein; M von Winterfeld; K Jöhrens; B Rau; S Daum; C Treese Journal: Oncoimmunology Date: 2020-09-30 Impact factor: 8.110