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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Wednesday, August 20, 2025
The addition of immune checkpoint inhibitors to chemotherapy, with or without antiangiogenic therapy, improved survival outcomes for patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC) with resistance to EGFR tyrosine kinase inhibitors (TKIs), according to the results of a meta-analysis published in JCO Precision Oncology. Select subgroups demonstrated even greater benefit, noted the research team.
The study authors, led by Letian Huang, MD, of the Department of Oncology, Shengjing Hospital of China Medical University in Shenyang, China, however, recommended careful monitoring for specific adverse events, as rates were significantly higher with the addition of immunotherapy across the eight randomized clinical trials included in the meta-analysis.
“Although this meta-analysis supports the potential benefit of adding immune checkpoint inhibitors to chemotherapy/antiangiogenic therapy particularly in certain subpopulations of EGFR TKI–resistant patients, it does not provide sufficient evidence to recommend this combination as a preferred or priority strategy for all patients after EGFR TKI resistance,” they wrote.
The researchers conducted a systematic review and meta-analysis of eight randomized controlled trials of immune checkpoint inhibitors added to chemotherapy with or without antiangiogenic therapy compared with chemotherapy/antiangiogenic therapy alone. The analysis included 10 cohorts and 2,269 participating patients with EGFR-mutant advanced NSCLC who were resistant to EGFR TKIs.
Overall, the addition of immune checkpoint inhibitors led to an improvement in progression-free survival (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.57–0.80; P < .001), overall survival (HR = 0.89; 95% CI = 0.79–0.99; P = .031), and objective response rate (risk ratio = 0.80; 95% CI = 0.74–0.88; P < .001) over chemotherapy/antiangiogenic therapy alone.
Subgroup analyses indicated that survival benefits from the addition of immunotherapy were even more pronounced in patients with high PD-L1 expression (≥ 50%), EGFR L858R mutations, absence of EGFR T790M mutations, and who had received pemetrexed-platinum treatment.
Although the rates of grade ≥ 3 adverse events were similar with or without added immunotherapy, rates of treatment discontinuation and rates for rash, hypothyroidism, and hypertension were significantly higher with added immunotherapy.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
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