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Meta-Analysis
. 2020 Aug 3;3(8):e2012534.
doi: 10.1001/jamanetworkopen.2020.12534.

Association of Sex, Age, and Eastern Cooperative Oncology Group Performance Status With Survival Benefit of Cancer Immunotherapy in Randomized Clinical Trials: A Systematic Review and Meta-analysis

Fang Yang  1 , Svetomir N Markovic  2 , Julian R Molina  2 , Thorvardur R Halfdanarson  2 , Lance C Pagliaro  2 , Ashish V Chintakuntlawar  2 , Rutian Li  1 , Jia Wei  1 , Lifeng Wang  1 , Baorui Liu  1 , Grzegorz S Nowakowski  3 , Michael L Wang  4 , Yucai Wang  3
Affiliations
Meta-Analysis

Association of Sex, Age, and Eastern Cooperative Oncology Group Performance Status With Survival Benefit of Cancer Immunotherapy in Randomized Clinical Trials: A Systematic Review and Meta-analysis

Fang Yang et al. JAMA Netw Open. .

Abstract

Importance: Sex, age, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) may affect immune response. However, the association of these factors with the survival benefit of cancer immunotherapy with immune checkpoint inhibitors (ICIs) remains unclear.

Objective: To assess the potential sex, age, and ECOG PS differences of immunotherapy survival benefit in patients with advanced cancer.

Data sources: PubMed, Web of Science, Embase, and Scopus were searched from inception to August 31, 2019.

Study selection: Published randomized clinical trials comparing overall survival (OS) in patients with advanced cancer treated with ICI immunotherapy vs non-ICI control therapy were included.

Data extraction and synthesis: Pooled OS hazard ratio (HR) and 95% CI for patients of different sex, age (<65 and ≥65 years) or ECOG PS (0 and ≥1) were calculated separately using a random-effects model, and the heterogeneity between paired estimates was assessed using an interaction test by pooling study-specific interaction HRs. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.

Main outcomes and measures: The difference in survival benefit of ICIs between sex, age (<65 vs ≥65 years), and ECOG PS (0 vs ≥1), as well as the difference stratified by cancer type, line of therapy, agent of immunotherapy, and immunotherapy strategy in the intervention arm.

Results: Thirty-seven phase 2 or 3 randomized clinical trials involving 23 760 patients were included. An OS benefit of immunotherapy was found for both men (HR, 0.75; 95% CI, 0.71-0.81) and women (HR, 0.79; 95% CI, 0.72-0.88); for both younger (<65 years: HR, 0.77; 95% CI, 0.71-0.83) and older (≥65 years: HR, 0.78; 95% CI, 0.72-0.84) patients; and for both patients with ECOG PS 0 (HR, 0.81; 95% CI, 0.73-0.90) and PS greater than or equal to 1 (HR, 0.79; 95% CI, 0.74-0.84). No significant difference of relative benefit from immunotherapy over control therapy was found in patients of different sex (P = .25, I2 = 19.02%), age (P = .94, I2 = 15.57%), or ECOG PS (P = .74, I2 = 0%). No significant difference was found in subgroup analyses by cancer type, line of therapy, agent of immunotherapy, and immunotherapy strategy in the intervention arm.

Conclusions and relevance: This meta-analysis found no evidence of an association of sex, age (<65 vs ≥65 years), or ECOG PS (0 vs ≥1) with cancer immunotherapy survival benefit. This finding suggests that the use of ICIs in advanced cancer should not be restricted to certain patients in sex, age, or ECOG PS categories.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Halfdanarson reported receiving personal fees from Curium, Terumo, Lexicon, and ScioScientific; serving as a consult or on an advisory board without personal compensation from Advanced Accelerator Applications and Ipsen; and receiving grants from Ipsen, Thermo Fisher Scientific, and Basilea outside the submitted work. Dr M. L. Wang reported receiving grants, personal fees, and nonfinancial support from Janssen, AstraZeneca, Acerta Pharma, Pharmacyclics, Kite Pharma, Celgene, and Loxo Oncology; grants and nonfinancial support from VelosBio, BeiGene, BioInvent, and Verastem; grants from Eli Lilly and Aviara; personal fees and nonfinancial support from Juno Therapeutics; and personal fees from Guidepoint Global and Pulse Biosciences outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Study Selection Process
HRs indicates hazard ratios; ICIs, immune checkpoint inhibitors.
See this image and copyright information in PMC

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