Clinical evidence for the prognostic impact of metformin in cancer patients treated with immune checkpoint inhibitors

Jinhai Shen; Xinqi Ye; Hui Hou; Yun Wang

doi:10.1016/j.intimp.2024.112243

Clinical evidence for the prognostic impact of metformin in cancer patients treated with immune checkpoint inhibitors

Int Immunopharmacol. 2024 May 11:134:112243. doi: 10.1016/j.intimp.2024.112243. Online ahead of print.

Authors

Jinhai Shen¹, Xinqi Ye¹, Hui Hou², Yun Wang³

Affiliations

¹ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China.
² State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China. Electronic address: 1020172549@cpu.edu.cn.
³ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China. Electronic address: wangyun@cpu.edu.cn.

PMID: 38735258
DOI: 10.1016/j.intimp.2024.112243

Abstract

Background: Preclinical studies suggest that metformin might enhance the efficacy of immune checkpoint inhibitors (ICIs) and potentially influence the prognoses of cancer patients undergoing ICIs treatment. This study endeavors to assess the prognostic significance of metformin in cancer patients undergoing ICIs therapy, aiming to furnish evidence-based insights for clinical practice.

Methods: A thorough literature search was conducted across electronic databases to encompass all potential records published before November 20th, 2023. A meta-analysis was executed utilizing Stata 17.0 to derive pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for both overall survival (OS) and progression-free survival (PFS).

Results: A total of 22 studies encompassing 9,011 patients met the inclusion criteria. Meta-analyses revealed a significant correlation between metformin use and poorer OS (HR, 1.13; 95 %CI, 1.04-1.23; P = 0.004) rather than PFS (HR, 1.04; 95 %CI, 0.96-1.14; P = 0.345) among cancer patients undergoing ICIs treatment. Subgroup analysis delineated that the concurrent administration of metformin and ICIs significantly associated with adverse prognoses in the European population (OS: HR, 1.23; 95 %CI, 1.10-1.39; P = 0.001; PFS: HR, 1.14; 95 %CI, 1.02-1.28; P = 0.024).

Conclusion: Based on current clinical evidence, concomitant metformin use does not appear to improve the prognostic outcomes for cancer patients undergoing ICIs therapy and may potentially correlate with inferior prognoses. Further studies are imperative to comprehensively elucidate the impact of metformin within the realm of ICIs therapy.

Keywords: Cancer; Immune checkpoint inhibitors; Meta-analysis; Metformin; Prognoses.