Correlation between patients' age and cancer immunotherapy efficacy

Qiong Wu; Qiuhong Wang; Xin Tang; Ran Xu; Luzhong Zhang; Xinming Chen; Qun Xue; Ziheng Wang; Rongfeng Shi; Feiran Wang; Fei Ju; Bo Zhang; You Lang Zhou

doi:10.1080/2162402X.2019.1568810

Correlation between patients' age and cancer immunotherapy efficacy

Oncoimmunology. 2019 Feb 3;8(4):e1568810. doi: 10.1080/2162402X.2019.1568810. eCollection 2019.

Authors

Qiong Wu^{1

2}, Qiuhong Wang², Xin Tang³, Ran Xu¹, Luzhong Zhang³, Xinming Chen⁴, Qun Xue⁴, Ziheng Wang^{5

6}, Rongfeng Shi⁷, Feiran Wang⁸, Fei Ju², Bo Zhang², You Lang Zhou²

Affiliations

¹ Medical school, Nantong university, Nantong, P.R. China.
² The Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, P.R. China.
³ Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, P.R. China.
⁴ Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, P.R. China.
⁵ Department of Medicine, Nantong University Xinling college, Nantong, Jiangsu, P.R. China.
⁶ Department of anesthesiology, The First people's Hospital of Taicang City, Taicang Affiliated Hospital of Soochow University, Suzhou, P.R. China.
⁷ Department of Interventional, Affiliated Hospital of Nantong University, Nantong, P.R. China.
⁸ Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, P.R. China.

Abstract

Background: Although immunosenescence-induced difference on overall immune function and immune cell subsets between younger and older populations has been well characterized, the potential effect of patients' age on the efficacy of immune checkpoint inhibitors (ICIs) remains little known. We performed a meta-analysis to investigate whether age differences play a role in cancer immunotherapy efficacy based on a large amount of clinical data. Methods: We conducted a systematic search of PubMed, Embase and MEDLINE for relevant randomized controlled trials. The primary outcome was overall survival (OS) and progression-free survival (PFS) was secondary outcome. The interaction test was used to assess the heterogeneity of HR between younger and older groups. Results: In total, 19 clinical randomized trials involving 11157 patients were included. The pooled HR for OS was 0.73 (95% CI 0.69-0.78) and 0.63 (95% CI 0.52-0.73) for PFS in younger patients receiving ICIs treatments, when compared with younger patients treated with controls. For older patients treated with ICIs, the pooled HR for OS compared with controls was 0.64 (95% CI 0.59-0.69) and 0.66 (95% CI 0.58-0.74) for PFS. The difference on OS efficacy between younger and older patients treated with ICIs was significant (P_{heterogeneity} = 0.025). Conclusions: Immune checkpoint inhibitors significantly improved OS and PFS in both younger and older patients compared with controls, but the magnitude of benefit was clinically age-dependent. Patients ≥65 y can benefit more from immunotherapy than younger patients. Future research should take age difference into consideration in trials and focus on tolerance and toxicity of ICIs in older patients.

Keywords: Immune checkpoint inhibitor; age; immunosenescence; overall survival; progression-free survival.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

This study was funded by the National Natural Science Foundation of China (No. 81401796 and 81572267), Key Research and Development Projects of Jiangsu Province (BE2017681), Six Talent Peaks Program of Jiangsu Province (WSW-038), Jiangsu Post-doctoral Program (1701008A), Jiangsu youth medical talent project (QNRC2016702) and China Post-doctoral program (2017M621800).