Impact of poor performance status on outcomes with immune checkpoint inhibitors in advanced non–small cell lung cancer: A systematic review and meta-analysis.

e20617 Background: Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced non–small cell lung cancer (NSCLC). However, patients with poor baseline performance status (ECOG ≥2) are commonly underrepresented in clinical trials, limiting the applicability of trial results to routine clinical practice. The prognostic significance of poor performance status in ICI-treated advanced NSCLC remains incompletely characterized. We conducted a systematic review and meta-analysis to evaluate the association between baseline ECOG performance status and survival outcomes in real-world patients receiving ICIs. Methods: We systematically identified observational and real-world studies reporting multivariable-adjusted hazard ratios (HRs for overall survival (OS) and/or progression-free survival (PFS) comparing ECOG ≥2 with ECOG 0–1 or < 2 in patients with advanced NSCLC treated with ICIs. Only studies with harmonizable ECOG contrasts and adjusted effect estimates were included in the quantitative synthesis. Hazard ratios were pooled on the logarithmic scale using the generic inverse-variance method. Random-effects models were applied using the DerSimonian–Laird estimator, with fixed-effect models calculated for comparison. Statistical heterogeneity was assessed using Cochran’s Q and the I² statistic. Results: Twenty studies met criteria for qualitative synthesis. Thirteen effect-size comparisons were eligible for quantitative analysis, including seven OS and six PFS evaluations. Across all OS studies, poor baseline performance status was consistently associated with inferior survival. Individual OS hazard ratios ranged from approximately 2.0 to nearly 4.0, indicating a substantially increased risk of death among patients with ECOG ≥2. In the random-effects model, ECOG ≥2 was associated with significantly worse OS (pooled HR 2.58, 95% CI 2.11–3.15), with moderate-to-substantial heterogeneity (I² = 70.0%). Six studies contributed to the PFS meta-analysis. In the random-effects model, poor performance status was associated with worse PFS (pooled HR 1.38, 95% CI 0.58–3.27), with substantial heterogeneity (I² = 95.2%). Conclusions: In real-world patients with advanced NSCLC treated with ICIs, poor baseline performance status is associated with significantly inferior overall survival and a trend toward worse progression-free survival. These findings highlight the prognostic importance of performance status in routine clinical practice and support the need for prospective studies and individualized treatment approaches for patients with impaired functional status.