638 Background: The role of immune checkpoint inhibitors (ICIs) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remains poorly defined. While single-institution studies and early-phase trials suggest occasional durable benefit, a consolidated synthesis is lacking. Methods: We searched PubMed, Cochrane, and ASCO/ESMO abstracts (inception-September 8, 2025) for clinical studies reporting ICI outcomes (objective response rate ORR, disease control rate DCR, survival, or grade ≥3 adverse events AEs) in GEP-NETs. Data were pooled using random-effects meta-analysis, with subgroup analyses by ICI class. Results: A total of 483 patients across 16 studies were included. Most patients had pancreatic NETs (42%) or GEP-NET not otherwise specified (35%); 53% were well-differentiated and 47% poorly differentiated/NEC. PD-1 inhibitors were the dominant class (85%), with 49% treated as monotherapy and 51% with combination regimens. Pooled ORR was 22.0% (95% CI, 12.5-35.9%). Pooled DCR was 52.8% (95% CI, 41.1-64.3%). Median overall survival was 13.9 months (IQR 7.2-24.2). PD-1 inhibitors achieved an ORR of 21.5%, PD-L1 inhibitors 6.2%, and PD-1/PD-L1 ± CTLA-4 regimens 18.8%. Disease control was highest with PD-1-based regimens (55%) and lowest with PD-L1 inhibitors (38%). Dual checkpoint blockade suggested enhanced activity but was limited by very small cohorts. Across studies, grade ≥3 AEs occurred in 30.2% of patients. Median follow-up was 20.4 months. Conclusions: ICIs show modest activity in GEP-NETs, with PD-1 regimens providing the most consistent benefit. Disease stabilization is common, but objective responses remain limited. Grade ≥3 toxicities occur in about one-third of patients. Dual checkpoint blockade shows preliminary activity but needs validation in larger cohorts given higher toxicity. These findings highlight the need for biomarker-driven selection and rational combinations to optimize outcomes. Pooled results. Domain Category/Finding Primary Site Pancreas (42.0%), GEP-NET NOS (35.0%), Small intestine (10.6%), Colon (3.9%), Stomach (3.3%), Rectum (3.1%), Others (≤0.8%) Differentiation Well-diff (52.6%), Poorly diff/NEC (47.2%), NR (6.4%) IO Class PD-1 inhibitors (85.3%), PD-L1 inhibitors (6.6%), PD-1/PD-L1 ± CTLA-4 (8.1%) Combination Pattern Monotherapy 49.3%, Dual ICI 29.6%, IO+Chemo 14.5%, IO+TKI 6.0%, IO+Other 0.6% Prior Therapy 1L: 15.5%; ≥2L: 73.1%; NR: 11.4% Median OS 13.9 mo (IQR: 7.2-24.2) Overall ORR 22.0% (95% CI 12.5-35.9%); I²=79.7% Overall DCR 52.8% (95% CI 41.1-64.3%); I²=71.0% Grade ≥3 AEs 30.2% (95% CI 19.8-43.1%); I²=80.9%
Sarfraz et al. (Sat,) studied this question.