A Multicenter Retrospective Study of the Combination of Immune Checkpoint Inhibitors and Chemotherapy Regimens with or Without Liver Metastasis for the First-line Treatment of Advanced Gastric Cancer

Overview

Journal Ther Adv Med Oncol

Specialty Oncology

Date 2024 Dec 23

PMID 39712075

Authors

Jing Ren

Ke Wang

Qianhao Meng

Chang Xu

Changqing Liu

Yusheng Wang

Guangyu Wang

Affiliations

Soon will be listed here.

Abstract

Background: Several studies have indicated that the use of immune checkpoint inhibitors (ICI) can prolong the survival of patients with advanced gastric cancer (AGC). However, it remains unclear whether the presence of liver metastasis leads to systemic immune suppression, resulting in poorer immune therapy outcomes. This study aims to investigate whether liver metastasis affects the efficacy of ICI in first-line treatment for AGC patients.

Methods: The data of AGC patients undergoing combined immunotherapy and chemotherapy treatment at Harbin Medical University Cancer Hospital and the First Hospital of Shanxi Medical University from January 2018 to January 2023 were collected. The Kaplan-Meier method and Cox proportional hazards regression analysis were employed to analyze the overall survival (OS) and progression-free survival (PFS) of the patients.

Results: A total of 162 patients with AGC who were human epidermal growth factor receptor 2 (Her 2) negative and treated with immunotherapy in the first line were included in the study. Patients were divided into two groups, the liver metastasis group (LM group, = 40) and the group without liver metastasis (NLM group, = 122) according to the presence of liver metastasis. The results of the present study indicate that there was no statistically significant difference in the median OS, with median OS of 17 and 15 months, respectively ( = 0.29). Similarly, no significant difference was observed in the median PFS between the two groups ( = 0.65).

Conclusion: This study suggests that the presence or absence of liver metastasis does not significantly affect the prognosis of AGC patients receiving first-line treatment with ICI.

References

Yukami H, Kawazoe A, Lin Y, Koyama S, Fukuoka S, Hara H . Updated Efficacy Outcomes of Anti-PD-1 Antibodies plus Multikinase Inhibitors for Patients with Advanced Gastric Cancer with or without Liver Metastases in Clinical Trials. Clin Cancer Res. 2022; 28(16):3480-3488. PMC: 9662898. DOI: 10.1158/1078-0432.CCR-22-0630. View

Yoon H, Jin Z, Kour O, Kankeu Fonkoua L, Shitara K, Gibson M . Association of PD-L1 Expression and Other Variables With Benefit From Immune Checkpoint Inhibition in Advanced Gastroesophageal Cancer: Systematic Review and Meta-analysis of 17 Phase 3 Randomized Clinical Trials. JAMA Oncol. 2022; 8(10):1456-1465. PMC: 9412834. DOI: 10.1001/jamaoncol.2022.3707. View

Motoo I, Ando T, Hamashima T, Kajiura S, Sakumura M, Ueda Y . Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer. Front Oncol. 2023; 13:1193533. PMC: 10542891. DOI: 10.3389/fonc.2023.1193533. View

Tumeh P, Harview C, Yearley J, Shintaku I, Taylor E, Robert L . PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515(7528):568-71. PMC: 4246418. DOI: 10.1038/nature13954. View

Digklia A, Wagner A . Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol. 2016; 22(8):2403-14. PMC: 4768187. DOI: 10.3748/wjg.v22.i8.2403. View

Loo K, Tsai K, Mahuron K, Liu J, Pauli M, Sandoval P . Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy. JCI Insight. 2017; 2(14). PMC: 5518562. DOI: 10.1172/jci.insight.93433. View

Liu T, Bai Y, Lin X, Li W, Wang J, Zhang X . First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric, gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis. Int J Cancer. 2022; 152(4):749-760. PMC: 10092493. DOI: 10.1002/ijc.34296. View

Hagi T, Kurokawa Y, Kawabata R, Omori T, Matsuyama J, Fujitani K . Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer. Br J Cancer. 2020; 123(6):965-972. PMC: 7492241. DOI: 10.1038/s41416-020-0975-7. View

Yoon H, Bendell J, Braiteh F, Firdaus I, Philip P, Cohn A . Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial. Ann Oncol. 2016; 27(12):2196-2203. PMC: 7360144. DOI: 10.1093/annonc/mdw423. View

10.

Castelo-Branco L, Pellat A, Martins-Branco D, Valachis A, Derksen J, Suijkerbuijk K . ESMO Guidance for Reporting Oncology real-World evidence (GROW). Ann Oncol. 2023; 34(12):1097-1112. DOI: 10.1016/j.annonc.2023.10.001. View

11.

Lee J, Mehdizadeh S, Smith J, Young A, Mufazalov I, Mowery C . Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis. Sci Immunol. 2020; 5(52). PMC: 7755924. DOI: 10.1126/sciimmunol.aba0759. View

12.

Saberzadeh-Ardestani B, Jones J, McWilliams R, Tougeron D, Halfdanarson T, Guimbaud R . Metastatic site and clinical outcome of patients with deficient mismatch repair metastatic colorectal cancer treated with an immune checkpoint inhibitor in the first-line setting. Eur J Cancer. 2023; 196:113433. DOI: 10.1016/j.ejca.2023.113433. View

13.

Janjigian Y, Shitara K, Moehler M, Garrido M, Salman P, Shen L . First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021; 398(10294):27-40. PMC: 8436782. DOI: 10.1016/S0140-6736(21)00797-2. View

14.

Qiu M, Shi S, Chen Z, Yu H, Sheng H, Jin Y . Frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from gastric cancer: A SEER-based study. Cancer Med. 2018; 7(8):3662-3672. PMC: 6089142. DOI: 10.1002/cam4.1661. View

15.

Bray F, Laversanne M, Sung H, Ferlay J, Siegel R, Soerjomataram I . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3):229-263. DOI: 10.3322/caac.21834. View

16.

Topalian S, Hodi F, Brahmer J, Gettinger S, Smith D, Mcdermott D . Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non-Small Cell Lung Cancer Treated With Nivolumab. JAMA Oncol. 2019; 5(10):1411-1420. PMC: 6659167. DOI: 10.1001/jamaoncol.2019.2187. View

17.

Xu J, Jiang H, Pan Y, Gu K, Cang S, Han L . Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial. JAMA. 2023; 330(21):2064-2074. PMC: 10698618. DOI: 10.1001/jama.2023.19918. View

18.

Tumeh P, Hellmann M, Hamid O, Tsai K, Loo K, Gubens M . Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC. Cancer Immunol Res. 2017; 5(5):417-424. PMC: 5749922. DOI: 10.1158/2326-6066.CIR-16-0325. View

19.

Garassino M, Cho B, Kim J, Mazieres J, Vansteenkiste J, Lena H . Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018; 19(4):521-536. PMC: 7771363. DOI: 10.1016/S1470-2045(18)30144-X. View

20.

Fuca G, Cohen R, Lonardi S, Shitara K, Elez M, Fakih M . Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers. J Immunother Cancer. 2022; 10(2). PMC: 8811606. DOI: 10.1136/jitc-2021-004001. View