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Characteristics and clinical outcomes of patients with advanced gastric or gastroesophageal cancer treated in and out of randomized clinical trials of first-line immune checkpoint inhibitors

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Abstract

Background

Although several randomized trials (RCTs) showed survival benefits of immune checkpoint inhibitor (ICI) plus first-line chemotherapy for advanced gastric or gastroesophageal cancer (AGC), these trials could enroll patients who fulfilled the strict eligibility criteria or waited for certain screening period for central assessment of PD-L1 status.

Methods

We retrospectively compared characteristics and clinical outcomes of the patients with AGC who received first-line chemotherapy in control arm of RCTs with ICIs (control group) or clinical practice (practice group) at our institution from February 2016 to April 2019.

Results

The control group had a better baseline Eastern Cooperative Oncology Group performance status (PS0, 81.2% vs. 51.4%, p < 0.001) and a longer interval from first visit to first-line chemotherapy initiation (19 days vs. 9 days, p < 0.001) than the practice group. Median overall survival (OS) was 20.3 months in control group and 15.7 months in practice group, with a trend of longer OS in control group than that in practice group (hazard ratio, 0.71; p = 0.062). More patients in control group were treated with subsequent chemotherapy including ICIs.

Conclusion

Patients with AGC in RCTs of ICIs had a better PS or a higher chance to receive subsequent chemotherapy, resulting in a better prognosis than those treated in clinical practice. This information should be considered when interpreting RCT results and applying new treatments into clinical practice.

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Data Availability

The evaluation data set analyzed in the current study is not available publicly. However, the data are available from the corresponding author on request.

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Acknowledgements

The authors thank all patients and families for participation in the studies, as well as colleagues. The authors also would like to thank Enago (www.enago.jp) for the English language review.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Yu Aoki, Akihito Kawazoe, Yohei Kubota, Keigo Chida, Saori Mishima, Daisuke Kotani, Yoshiaki Nakamura, Yasutoshi Kuboki, Hideaki Bando, Takashi Kojima, Toshihiko Doi, Takayuki Yoshino & Kohei Shitara

  2. Division of Gastroenterology and Hepatology of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yu Aoki

  3. Department of Gastroenterology, Tsuchiura Kyodo General Hospital, 4-1-1 Otsuno, Tsuchiura, Ibaraki, 300-0028, Japan

    Yohei Kubota

  4. Translational Research Support Section, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Yoshiaki Nakamura

  5. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Takeshi Kuwata

  6. Department of Immunology, Nagoya University Graduate School of Medicine, 65 tsurumai-cho, showa-ku, Nagoya, Aichi, 466-8550, Japan

    Kohei Shitara

Authors
  1. Yu Aoki
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  2. Akihito Kawazoe
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  3. Yohei Kubota
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  4. Keigo Chida
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  5. Saori Mishima
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  6. Daisuke Kotani
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  7. Yoshiaki Nakamura
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  8. Yasutoshi Kuboki
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  9. Hideaki Bando
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  10. Takashi Kojima
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  11. Toshihiko Doi
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  12. Takayuki Yoshino
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  13. Takeshi Kuwata
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  14. Kohei Shitara
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Contributions

Yu Aoki, Akihito Kawazoe, and Kohei Shitara contributed to the study conception, design, data analysis and interpretation. Material preparation and data collection were performed by Yu Aoki and Yohei Kubota. The first draft of the manuscript was written by Yu Aoki and Kohei Shitara. All authors commented on previous versions of the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Kohei Shitara.

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Conflict of interest

Yu Aoki declares no conflict of interest. Akihito Kawazoe reports honoraria from Daiichi Sankyo, Lilly, Ono, Taiho, Bristol Myers Squibb, and Merck Seronobiopharma: research funding from Ono, MSD, Taiho, Bayer, Sumitomo Dainippon and AstraZeneca. Yohei Kubota reports receiving research funding from Astellas. Keigo Chida reports honoraria from Bayer. Saori Mishima reports honoraria from Merck Seronobiopharma: research funding from Roche Diagnostics. Daisuke Kotani reports honoraria from Takeda, Chugai, Lilly, MSD, Ono, Taiho, Bristol Myers Squibb, and Merckbiopharma: research funding from Ono, MSD, Novartis, Servier, Janssen, IQVIA, Syneoshealth, and Cimicshiftzero. Yoshiaki Nakamura reports honoraria from Guardant Health Inc., Merck Pharmaceutical, and Chugai Pharmaceutical: research funding from Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Guardant Health Inc., Genomedia Inc., Roche Diagnostics, Seagen outside the submitted work. Yasutoshi Kuboki reports receiving personal fees for advisory roles from Takeda, Boehringer Ingelheim, and Taiho: receiving honoraria (lecture fee) from ONO, Bayer, and Sanofi; and receiving research funding from Taiho, Takeda, ONO, Abbie, AstraZeneca, Boehringer Ingelheim, Incyte, Amgen, Chugai, GSK, Genmab, Astelas, and Daiichi-Sankyo, outside the submitted work. Hideaki Bando reports honoraria from Taiho Pharmaceutical, Eli Lilly Japan, and Ono Pharmaceutical: research funding from Ono Pharmaceutical and Chugai Pharmaceutical outside the submitted work. Takashi Kojima reports grants and personal fees from Ono Pharmaceutical and MSD, grants from Astellas Amgen BioPharma, Taiho Pharmaceutical and Shionogi, personal fees from Oncolys BioPharma, Astellas Pharma, BMS and Merk. Toshihiko Doi reports receiving personal fee for advisory roles from Boehringer Ingelheim, Janssen Pharmaceutical, Rakuten Medical, Amgen, MSD, Otsuka Pharmaceutical, Kyowa Kirin, Daiichi Sankyo, Sumitomo Dainippon, Abbvie, Takeda Pharmaceutical; receiving honoraria (lecture fee) from Ono Pharmaceutical, BMS and receiving research funding from TAIHO PHARMACEUTICAL, Novartis, MSD, Janssen Pharmaceutical, Boehringer Ingelheim, Eisai, Pfizer, Sumitomo Dainippon, Chugai Pharmaceutical, Daiichi Sankyo, BMS, Abbvie, Lilly, IQVIA, Merck Serono, outside the submitted work. Takayuki Yoshino reports honoraria from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly Japan, Merck Biopharma, Bayer Yakuhin, Ono Pharmaceutical and MSD; and receiving research funding from Ono Pharmaceutical, Sanofi, Daiichi Sankyo, PAREXEL International, Pfizer Japan, Taiho Pharmaceutical, MSD, Amgen, Genomedia Inc., Sysmex, Chugai Pharmaceutical and Nippon Boehringer Ingelheim, outside the submitted work. Takeshi Kuwata report honoraria from AstraZeneca, Celltrion, Astellas Pharma, MSD, Bristol-Myers Squibb Japan and Ono Pharmaceutical: Research funding from Roche Diagnostics Japan, Daiichi Sankyo and Ono Pharmaceutical. Kohei Shitara reports receiving personal fees for advisory roles from Lilly, Bristol Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical, Merck Pharmaceutical, Taiho Pharmaceutical, Novartis, AbbVie, GlaxoSmithKline, Daiichi Sankyo, Amgen, Boehringer Ingelheim, and Janssen; receiving honoraria (lecture fee) from Takeda and Bristol-Myers Squibb; and receiving research funding from Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai, MSD, Medi Science, Eisai and Amgen, outside the submitted work.

Consent to participate

Informed consent requirement was waived due to the study's observational retrospective design, with an opt-out opportunity provided at the institution's website.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional review board of the National Cancer Center Japan (No.2017-120).

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Aoki, Y., Kawazoe, A., Kubota, Y. et al. Characteristics and clinical outcomes of patients with advanced gastric or gastroesophageal cancer treated in and out of randomized clinical trials of first-line immune checkpoint inhibitors. Int J Clin Oncol 27, 1413–1420 (2022). https://doi.org/10.1007/s10147-022-02200-1

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  • DOI: https://doi.org/10.1007/s10147-022-02200-1

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