Impact of baseline performance status on survival and toxicity with ipilimumab plus nivolumab: A 10-year institutional experience across solid tumors.

Abstract

e23340 Background: Dual immune checkpoint blockade with ipilimumab plus nivolumab (Ipi+Nivo) provides durable benefit across multiple solid tumors and is increasingly used in routine practice. However, patients with poor performance status (PS) are largely excluded from immunotherapy trials, limiting the generalizability of these results to this population. In a prior small institutional analysis, we observed significantly worse overall survival in patients with poor PS compared with good PS. Building on this work, we analyzed a decade-long institutional cohort to evaluate survival, response, toxicity, and hospitalization outcomes with Ipi+Nivo across advanced solid tumors, stratified by baseline PS. Methods: We conducted a retrospective cohort study of adults with advanced/metastatic solid tumors treated with Ipi+Nivo at an NCI-designated cancer center between January 2014 and January 2025. Patients were stratified by baseline ECOG PS into good (0–1) and poor (≥2) groups. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), grade 3-4 immune-related adverse events (irAEs), and hospitalization. Survival was estimated using Kaplan-Meier methods and multivariable time-dependent Cox regression. Multivariable logistic regression was used for secondary outcomes. Results: Among 270 patients, 219 (81%) had ECOG PS 0–1 and 51 (19%) had ECOG PS ≥2. Median OS was significantly shorter in patients with poor PS compared with good PS (4.6 vs 21.2 months; p<0.001). In multivariable time-dependent analyses, poor PS was associated with a markedly increased mortality risk at treatment initiation (Hazard Ratio=4.36), with attenuation of this effect over time (p=0.047). ORR was lower in the poor PS group (18% vs 36%; p=0.013). Patients with poor PS had higher baseline neutrophil-to-lymphocyte ratios (NLR; median 6.6 vs 4.3; p=0.001). Grade 3-4 irAEs were less frequent in poor PS patients (29% vs 51%; p=0.005), yet hospitalization occurred more often (78% vs 58%; p=0.007), with higher admission frequency. Conclusions: In a large cohort, patients with advanced malignancies and poor PS treated with Ipi+Nivo had markedly worse survival and response rates and substantially higher hospitalization despite fewer severe irAEs. These results highlight a disconnect between toxicity and clinical benefit, identify poor performance status as a marker of limited clinical benefit from dual immune checkpoint blockade, and underscore the need for improved patient selection and alternative therapeutic strategies in this high-risk population. Key clinical outcomes. Outcome ECOG 0–1 (n = 219) ECOG ≥2 (n = 51) p-value Median OS, months 21.2 4.6 <0.001 ORR (CR + PR), % 36% 18% 0.013 Grade 3–4 IrAEs, % 51% 29% 0.005 Any Hospitalization, % 58% 78% 0.007 Baseline NLR (IQR) 4.3 (2.4–6.7) 6.6 (3.5–10.6) 0.001