Clinical Trial

. 2023 Sep;54(3):951-961.

doi: 10.1007/s12029-023-00920-9. Epub 2023 Apr 10.

Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer

Kei Muro¹, Kohei Shitara², Kensei Yamaguchi³, Takaki Yoshikawa⁴, Hironaga Satake^{5

6}, Hiroki Hara⁷, Naotoshi Sugimoto⁸, Nozomu Machida⁹, Masahiro Goto¹⁰, Hisato Kawakami¹¹, Kenji Amagai¹², Yasushi Omuro¹³, Taito Esaki¹⁴, Shuichi Hironaka¹⁵, Tomohiro Nishina¹⁶, Yoshito Komatsu¹⁷, Hisahiro Matsubara¹⁸, Shinichi Shiratori¹⁹, Shirong Han¹⁹, Taroh Satoh²⁰, Atsushi Ohtsu²¹

Affiliations

¹ Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusaku, Nagoya, 464-8681, Japan. kmuro@aichi-cc.jp.
² Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
³ Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto City, Japan.
⁴ Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.
⁵ Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
⁶ Department of Medical Oncology, Kochi Medical School, Kochi, Japan.
⁷ Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan.
⁸ Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁹ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁰ Cancer Chemotherapy Center, Osaka Medical College, Osaka, Japan.
¹¹ Medical Oncology, Kindai University, Osaka, Japan.
¹² Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Kasama, Japan.
¹³ Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Bunkyo City, Japan.
¹⁴ Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
¹⁵ Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
¹⁶ Clinical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
¹⁷ Department of Cancer Chemotherapy, Division of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
¹⁸ Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
¹⁹ Oncology Clinical Development, MSD K.K, Tokyo, Japan.
²⁰ Department of Frontier Science for Cancer and Chemotherapy, Osaka University Hospital, Suita, Osaka, Japan.
²¹ Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

PMID: 37037952
PMCID: PMC10613141
DOI: 10.1007/s12029-023-00920-9

Clinical Trial

Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer

Kei Muro et al. J Gastrointest Cancer. 2023 Sep.

. 2023 Sep;54(3):951-961.

doi: 10.1007/s12029-023-00920-9. Epub 2023 Apr 10.

Authors

Affiliations

¹ Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusaku, Nagoya, 464-8681, Japan. kmuro@aichi-cc.jp.
² Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
³ Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto City, Japan.
⁴ Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.
⁵ Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
⁶ Department of Medical Oncology, Kochi Medical School, Kochi, Japan.
⁷ Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan.
⁸ Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁹ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁰ Cancer Chemotherapy Center, Osaka Medical College, Osaka, Japan.
¹¹ Medical Oncology, Kindai University, Osaka, Japan.
¹² Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Kasama, Japan.
¹³ Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Bunkyo City, Japan.
¹⁴ Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
¹⁵ Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
¹⁶ Clinical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
¹⁷ Department of Cancer Chemotherapy, Division of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
¹⁸ Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
¹⁹ Oncology Clinical Development, MSD K.K, Tokyo, Japan.
²⁰ Department of Frontier Science for Cancer and Chemotherapy, Osaka University Hospital, Suita, Osaka, Japan.
²¹ Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

PMID: 37037952
PMCID: PMC10613141
DOI: 10.1007/s12029-023-00920-9

Abstract

Purpose: Pembrolizumab demonstrated antitumor activity in programmed death ligand 1 positive (combined positive score (CPS) ≥ 1) gastric/gastroesophageal junction cancer in KEYNOTE-059 (third line or beyond), KEYNOTE-061 (second line), and KEYNOTE-062 (first line). We characterized efficacy and safety of pembrolizumab monotherapy in Japanese patients across several lines of therapy in these studies.

Methods: This analysis was conducted in 34 patients from KEYNOTE-059 cohort 1 (all pembrolizumab), including 13 patients with CPS ≥ 1, 65 patients with CPS ≥ 1 from KEYNOTE-061 (pembrolizumab, n = 27; chemotherapy, n = 38), and 70 patients with CPS ≥ 1 from KEYNOTE-062 (pembrolizumab, n = 38; chemotherapy, n = 32). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were evaluated.

Results: In KEYNOTE-059, ORR with pembrolizumab was 9%, median PFS was 2 months, and median OS was 10 months. In KEYNOTE-061, median OS was 12 months with pembrolizumab versus 10 months with chemotherapy (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.39-1.15). Median PFS (pembrolizumab vs. chemotherapy) was 2 months versus 4 months (HR, 1.21; 95% CI, 0.69-2.13); ORR was 7% versus 18%. In KEYNOTE-062, median OS was 20 months with pembrolizumab versus 18 months with chemotherapy (HR, 0.76; 95% CI, 0.43-1.33). Median PFS (pembrolizumab vs. chemotherapy) was 6 months versus 7 months (HR, 1.03; 95% CI, 0.61-1.74); ORR was 29% versus 34%.

Conclusions: The current analysis provides valuable information that anti-PD-1 therapies are worthy of further assessment for gastric cancer.

Trial registration: ClinicalTrials.gov: NCT02335411 (KEYNOTE-059), NCT02370498 (KEYNOTE-061), and NCT02494583 (KEYNOTE-062).

Keywords: Biomarkers; Clinical trial; Gastrointestinal neoplasm; Japan; Pembrolizumab.

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Conflict of interest statement

KM has received grants from Sanofi, Astellas, Amgen, Solasia Pharma, Daiichi Sankyo, Parexel International, Taiho Pharmaceutical, MSD K. K., Merck Serono, Pfizer, and Ono; has received honoraria from Eli Lilly, Chugai Pharmaceutical, Takeda, Ono, Taiho Pharmaceutical, Sanofi, Bristol Myers Squibb, and Bayer; and has participated on data safety monitoring board or advisory board for AstraZeneca and Ono. KS has received grants from MSD K. K., Astellas, Lilly, Ono, Dainippon Sumitomo, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD K.K., Mediscience, and Eisai; consulting fees from Astellas, Lilly, Bristol Myers Squibb, Takeda, Pfizer, Ono, MSD K.K., Taiho Pharmaceutical, Novartis, AbbVie, GSK, Daiichi Sankyo, Amgen, and Boehringer Ingelheim; and honoraria from Novartis, AbbVie, and Yakult Honsha. KY reports no conflict of interest. TY has received consulting fees from MSD K. K. and honoraria for lectures from MSD K. K., Ono, and Bristol Myers Squibb. HS has received grants from Taiho Pharmaceutical, Chugai Pharmaceutical, and Yakult Honsha; consulting fees from Bristol Myers Squibb; and honoraria from Bristol Myers Squibb, Taiho Pharmaceutical, MSD K.K., Chugai Pharmaceutical, and Yakult Honsha. HH has received funding for medical writing assistance from MSD K.K.; grants from Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Elevar Therapeutics, GSK, Incyte, Merck Biopharma, MSD K. K., Ono, Pfizer, and Taiho Pharmaceutical; consulting fees from Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo, Lilly, MSD K. K., and Ono; and honoraria from Bayer, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly, Merck Biopharma, MSD K. K., Ono, Sanofi, Taiho Pharmaceutical, Takeda, and Yakult Honsha. NS’s institution has received funds from MSD K. K., Astellas, Solasia Pharma, Daiichi Sankyo, and Ono. NM has received honoraria from Ono, Taiho Pharmaceutical, Lilly, Daiichi Sankyo, Takeda, Bristol Myers Squibb, and Yakult Honsha. MG reports no conflict of interest. K has received grants from Chugai Pharmaceutical, Taiho Pharmaceutical, and Eisai; honoraria from Bristol Myers Squibb, AstraZeneca, Bayer Yakuhin, Eli Lilly, MSD K. K., Ono, Chugai Pharmaceutical, Daiichi Sankyo, Takeda, and Taiho Pharmaceutical; and consulting fees from Bristol Myers Squibb, Eli Lilly, MSD K. K., Ono, Daiichi Sankyo, and Taiho Pharmaceutical. KA reports no conflict of interest. YO has received grants from MSD K. K., Ono, BeiGene, Astellas, and Daiichi Sankyo. TE has received grants (paid to the institution) from MSD K. K., Novartis, Dainippon Sumitomo, Ono, Daiichi Sankyo, Astellas, Astellas Amgen Biopharma, BeiGene, Pierre Fabre Medicament, Ignyta, Array BioPharma, and Merck Serono and honoraria from MSD K. K., Ono, Daiichi Sankyo, Merck Serono, Eli Lilly, Taiho Pharmaceutical, Chugai Pharmaceutical, Sanofi, Takeda, and Bayer. SH has received grants from Taiho Pharmaceutical, Chugai Pharmaceutical, and Yakult Honsha; consulting fees from Bristol Myers Squibb; and honoraria from Ono, Eli Lilly, Daiichi Sankyo, Bristol Myers Squibb, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD K. K., and Yakult Honsha. TN has received personal fees from Ono, Taiho Pharmaceutical, Takeda, Chugai Pharmaceutical, and Daiichi Sankyo and grants from MSD K. K. YK has received grants from Taiho Pharmaceutical, Chugai Pharmaceutical, Takeda, Bayer Yakuhin, Sanofi-Aventis S. A., Ono, MSD K. K., Yakult Honsha, NanoCarrier, QuintilesIMS, SYSMEX Corp., Mediscience Planning Inc., Dainippon Sumitomo, Kyowa Kirin, Asahi Kasei Pharma, Nippon Zo Pharmaceutical, A2 Healthcare Corp., Daiichi Sankyo, Eisai, Parexel International Corp., Astellas, Incyte, Syneos Health, and IQVIA and personal fees from Taiho Pharmaceutical; Chugai Pharmaceutical; Takeda; Bayer Yakuhin; Sanofi-Aventis S. A.; Ono; Yakult Honsha; Daiichi Sankyo; EA Pharma Co., Ltd.; Eli Lilly Japan K. K.; Nipro Corp.; Bristol Myers Squibb; Moroo; Pfizer; Merck Biopharma; Medical Review Co., Ltd.; Sawai Pharmaceutical; Shiseido; Mitsubishi Tanabe; Nippon Kayaku; Shire Japan K. K.; and Novartis Pharma K. K. HM reports no conflict of interest. SS is an employee of MSD K.K., Tokyo, Japan and a stockholder in Merck & Co., Inc., Rahway, NJ, USA. SH reports no conflict of interest. TS has received grants from MSD K. K., Ono, Yakult Honsha, Chugai Pharmaceutical, Gilead, BeiGene, Eli Lilly, and Taiho Pharmaceutical; honoraria from Ono, Yakult Honsha, Chugai Pharmaceutical, Eli Lilly, and Taiho Pharmaceutical; and consulting fees from Takara-Bio. AO reports no conflict of interest.

Figures

**Fig. 1**
Kaplan–Meier estimates of overall survival in Japanese patients from a KEYNOTE-059 cohort 1, b KEYNOTE-061, and c KEYNOTE-062. *CPS* combined positive score

**Fig. 2**
Kaplan–Meier estimates of progression-free survival in Japanese patients from a KEYNOTE-059 cohort 1, b KEYNOTE-061, and c KEYNOTE-062. *CPS* combined positive score

See this image and copyright information in PMC

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Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer

Affiliations

Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical

Research Materials