Meta-analysis of Overall Survival With Immunotherapy in Patients With Advanced Cancer According to Sex, Age, and Performance Status

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In a systematic review and meta-analysis reported in JAMA Network Open, Yang et al found overall survival benefits with immune checkpoint inhibitor treatment vs non–immune checkpoint inhibitor treatment of advanced cancers irrespective of sex, age < 65 years vs ≥ 65 years, or Eastern Cooperative Oncology Group (ECOG) performance status of 0 vs ≥ 1.

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Study Details

Randomized clinical trials comparing overall survival in patients with advanced cancer who were treated with immune checkpoint inhibitors vs non–immune checkpoint inhibitor control therapy published through August 2019 were included in the analysis. Pooled overall survival hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated separately for patients of different sex, age (< 65 and ≥ 65 years), and ECOG performance status (0 and ≥ 1). The I2 statistic was used to quantify heterogeneity among the studies, with values of 25% indicating low; 50%, moderate; and 75%, high degrees of heterogeneity.

Key Findings

A total of 37 phase II or III (n = 34) randomized trials involving 23,760 patients were included in the analysis. Of these, 15 trials evaluated immune checkpoint inhibitors as first-line therapy. The most common cancer types included were non–small cell lung cancer (NSCLC; n = 14) and melanoma (n = 5). The most common immune checkpoint inhibitors used were PD-1/PD-L1 inhibitors (n = 27).

Overall survival benefit with immune checkpoint inhibitor treatment 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). No significant difference in relative benefit was found for men vs women (P = .25, I2 = 19.02%).

Survival benefit associated with immune checkpoint inhibitor treatment was found for both patients aged < 65 years (HR = 0.77, 95% CI = 0.71–0.83) and those aged ≥ 65 years (HR = 0.78, 95% CI = 0.72–0.84). No significant difference in relative benefit was observed according to age (P = .94, I2 = 15.57%).

Survival benefit was observed for both patients with ECOG performance status of 0 (HR = 0.81, 95% CI = 0.73–0.90) and for those with a performance status of ≥ 1 (HR = 0.79, 95% CI = 0.74–0.84). No significant difference in relative benefit was observed according to performance status (P = .74, I2 = 0%).

For each of the analyses according to sex, age, and performance status, no significant differences in the survival benefit of immune checkpoint inhibitor therapy vs control therapy were found in subgroup analyses by cancer type (NSCLC, melanoma, gastric cancer, or other); line of therapy (first or subsequent); immunotherapy agent (CTLA-4 inhibitor or PD-1/PD-L1 inhibitor); or intervention therapy (immune checkpoint inhibitor alone or with a non–immune checkpoint inhibitor agent).

The investigators concluded: “This meta-analysis found no evidence of an association of sex, age (< 65 vs ≥ 65 years), or ECOG performance status (0 vs ≥ 1) with cancer immunotherapy survival benefit. This finding suggests that the use of immune checkpoint inhibitors in advanced cancer should not be restricted to certain patients in sex, age, or ECOG performance status categories.”

Yucai Wang, MD, PhD, of the Division of Hematology, Mayo Clinic, Rochester, is the corresponding author for the JAMA Network Open article.

Disclosure: For full disclosures of the study authors, visit