Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06)

Sung Hee Lim; Keun-Wook Lee; Jae-Joon Kim; Hyeon-Su Im; In-Ho Kim; Hye Sook Han; Dong-Hoe Koo; Jang Ho Cho; Chi Hoon Maeng; Min-Young Lee; Hyo Jin Lee; Jwa Hoon Kim; Sang Gon Park; Joo Young Jung; Seong-Hoon Shin; Ki Hyang Kim; Hyeyeong Kim; So Yeon Oh; Minsu Kang; Minkyu Jung; Sun Young Rha

doi:10.1186/s12885-024-11972-w

Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06)

BMC Cancer. 2024 Feb 23;24(1):252. doi: 10.1186/s12885-024-11972-w.

Authors

Sung Hee Lim^{1

2}, Keun-Wook Lee^#³, Jae-Joon Kim⁴, Hyeon-Su Im⁵, In-Ho Kim⁶, Hye Sook Han⁷, Dong-Hoe Koo⁸, Jang Ho Cho⁹, Chi Hoon Maeng¹⁰, Min-Young Lee¹¹, Hyo Jin Lee¹², Jwa Hoon Kim¹³, Sang Gon Park¹⁴, Joo Young Jung¹⁵, Seong-Hoon Shin¹⁶, Ki Hyang Kim¹⁷, Hyeyeong Kim⁵, So Yeon Oh⁴, Minsu Kang¹⁸, Minkyu Jung¹⁹, Sun Young Rha^#²⁰

Affiliations

¹ Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul, South Korea.
² Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea.
³ Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. imdoctor@snu.ac.kr.
⁴ Department of Internal Medicine, School of Medicine, Pusan National University Yangsan Hospital, Pusan National University, Yangsan, Republic of Korea.
⁵ Department of Hematology and Oncology, Ulsan University Hospital, Ulsan University College of Medicine, Ulsan, South Korea.
⁶ Division of Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
⁷ Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea.
⁸ Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁹ Division of Oncology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
¹⁰ Division of Hematology-Oncology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, South Korea.
¹¹ Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, South Korea.
¹² Division of Hemato-Oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea.
¹³ Department of Internal Medicine, Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
¹⁴ Department of Hemato-Oncology, Chosun University Hospital, Gwangju, South Korea.
¹⁵ Division of Hemato-Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, South Korea.
¹⁶ Department of Hemato/Oncology, Internal Medicine, Kosin University Gospel Hospital, Busan, South Korea.
¹⁷ Division of Oncology, Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, Busan, South Korea.
¹⁸ Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
¹⁹ Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System, Seoul, South Korea.
²⁰ Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System, Seoul, South Korea. rha7655@yuhs.ac.

^# Contributed equally.

Abstract

Background: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC.

Methods: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan).

Results: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy.

Conclusions: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.

Trial registration: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

Keywords: Gastric cancer; Irinotecan; Nivolumab; Pembrolizumab; Third-line treatment.

Publication types

Multicenter Study

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
B7-H1 Antigen
Camptothecin
Fluorouracil
Humans
Immune Checkpoint Inhibitors / adverse effects
Irinotecan
Leucovorin
Niacinamide / analogs & derivatives*
Peritoneal Neoplasms* / drug therapy
Republic of Korea / epidemiology
Retrospective Studies
Stomach Neoplasms* / pathology

Substances

Irinotecan
Immune Checkpoint Inhibitors
B7-H1 Antigen
Camptothecin
homocysteine-thiolactone-nicotinamide
Fluorouracil
Leucovorin
Niacinamide