Baseline ECOG Performance Status 0 Versus 1 as a Modifier of Treatment Benefit from Adding an Immune Checkpoint Inhibitor to Chemotherapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) added to chemotherapy are established in solid tumors, but most trials enroll patients with ECOG performance status (PS) 0-1 patients. Whether baseline PS modifies the relative benefit of adding an ICI has not been formally tested using a within-trial interaction analysis. METHODS: Following PRISMA 2020 and AMSTAR-2, we searched five databases (inception to August 2026) for randomized trials of ICI plus chemotherapy versus chemotherapy alone reporting OS or PFS by baseline ECOG PS. Data pooled using random-effects meta-analysis; effect modification was tested using a within-trial interaction (ratio-of-hazard-ratios) method. Risk of bias used Cochrane RoB 2; certainty used GRADE. RESULTS: Seventy-four trials (43,157 patients) were included. ICI addition reduced mortality (PS 0: HR 0.78, 95% CI 0.75-0.83, 60 trials; PS ≥1: HR 0.77, 95% CI 0.74-0.79, 61 trials) and progression or death (PS 0: HR 0.62, 95% CI 0.58-0.66; PS ≥1: HR 0.64, 95% CI 0.60-0.67; 57 trials each). Interaction testing showed no OS difference by PS (HR_interaction 1.01, 95% CI 0.95-1.07, p=0.73) but significant PFS difference favoring PS 0 (HR_interaction 0.93, 95% CI 0.87-0.99, p=0.019). Certainty was high for OS/PS≥1, moderate for OS/PS0, and low for PFS. CONCLUSIONS: Adding an ICI to chemotherapy improved OS regardless of baseline PS, with no evidence of relative-OS effect modification. A modest, significant PFS interaction favored PS 0. ICI-chemotherapy should not be withheld from eligible PS 1 patients on PS alone; findings do not extend to PS ≥2 or address toxicity.