Disparities persist in NSCLC immunotherapy trials, new meta-analysis finds

Immune checkpoint inhibitors have helped change the trajectory of metastatic non-small cell lung cancer (NSCLC), but questions remain about whether their benefits extend evenly across all patient populations. A new systematic review and meta-analysis suggests that, at least in recent phase 3 trials, survival benefits appear similar by sex and age, while racial differences and gaps in representation persist.

Published December 30, 2025, in Cancers, the analysis was led by Adam Barsouk, M.D., resident physician and oncology researcher at the University of Pennsylvania. The researchers found that Asian patients enrolled in NSCLC immunotherapy trials experienced better survival than White patients, while Black patients were underrepresented to the point that meaningful subgroup survival analyses could not be performed.

NSCLC, the most common form of lung cancer, remains a leading cause of cancer-related death worldwide. Over the past decade, immune checkpoint inhibitors targeting PD-1, PD-L1 or CTLA-4 have become a mainstay of treatment for metastatic disease, often paired with chemotherapy. These immunotherapies have delivered meaningful survival gains overall, but questions remain about whether those benefits are shared evenly across populations that differ by age, sex and race. The PD-1 inhibitors include Opdivo (nivolumab), Keytruda (pembrolizumab) and Libtayo (cemiplimab). Tecentriq (atezolizumab) and Imfinzi (durvalumab) target PD-L1, and Yervoy (ipilimumab and Imjudo (tremelimumab) block CTLA-4.

To better understand whether survival benefits differ by demographic factors, the investigators conducted a comprehensive review of phase 3 prospective immunotherapy trials in metastatic NSCLC initiated after 2015. Using PubMed and ClinicalTrials.gov, they identified 21 trials encompassing 10,950 patients. Only studies that reported overall survival data by age, sex or race were included. The team then used random-effects meta-analyses to examine treatment effects across subgroups.

The results showed no statistically significant differences in overall survival benefit from immunotherapy when comparing men with women or patients younger than 65 with those 65 and older. However, point estimates suggested a modestly smaller benefit for women and older adults, raising questions that the authors say warrant further study with more inclusive data.

“These data are reassuring,” Barsouk said, noting that historically, survival disparities have been reported for women and older adults with metastatic NSCLC. “We did not observe those disparities in our study of recent data.”

Racial differences, however, were more striking. Asian patients showed better survival outcomes than White patients both when treated with immunotherapy and across all trial arms. Notably, no included trials reported survival subgroup analyses for Black patients, who accounted for roughly 1.5% of patients with reported race.

“Not enough Black patients were included in these trials to meaningfully analyze survival,” Barsouk said. That remains a major limitation of the current evidence base.

Rather than pointing to definitive biological differences, the authors emphasized that their findings highlight ongoing shortcomings in trial design and reporting. Barsouk added that further research is needed to clarify whether social factors, biology or differences in access to care contribute to improved outcomes observed among Asian patients.

They noted that many of the Asian patients included in the analysis came from trials conducted predominantly in Asian populations, where enrollment was intentionally designed to explore potential racial differences in treatment response. Similar efforts, the authors argued, are needed to improve inclusion of Black and other underrepresented groups in future studies.

The authors concluded that improving diversity in trial enrollment and standardizing subgroup reporting are essential to ensuring that the benefits of immunotherapy in metastatic NSCLC are evaluated and delivered more equitably across patient populations.