e16330 Background: Optimal sequencing of peptide receptor radionuclide therapy (PRRT) following progression on somatostatin analogues (SSAs) in patients with neuroendocrine tumors (NETs) remains undetermined. Comparative data to guide timing of PRRT relative to other therapies are limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including patients with metastatic G1-G2 well-differentiated NETs of gastroenteropancreatic origin who received SSAs as first-line therapy. Two cohorts were compared: (1) patients who received PRRT as second-line therapy without any prior systemic treatment (P2), and (2) patients who received other systemic therapies followed by PRRT (PX). Propensity score matching for baseline characteristics was performed to maintain parity. Primary outcome was overall survival (OS). Secondary analyses included treatment-related toxicities using diagnosis and laboratory-based adverse event signals within 12 months of index therapy. Results: A total of 4755 patients were included (P2: n = 3773; PX: n = 982). Approximately 80% of patients in both cohorts were Non-Hispanic White with Black patients representing around 12% in each group. Patients receiving PRRT after SSA failure without other intervening systemic treatments demonstrated improved survival outcomes compared with those receiving PRRT after other systemic therapies. The survival probability was 79.31% in P2 vs 70.48% in PX at the end of 5 years (p < 0.001), 65.75% in P2 vs 43.23% in PX at the end of 10 years (p < 0.001). Median OS favored second-line PRRT, with consistent benefit across sensitivity analyses. Toxicity analyses revealed that P2 showed lower rates of anemia, thrombocytopenia, neutropenia, and renal injury compared with PX, while rates of liver enzyme elevation were similar in both groups. Conclusions: In this large real-world analysis, use of PRRT earlier in the treatment sequence following SSA progression was associated with improved clinical outcomes and a favorable toxicity profile. These findings support consideration of PRRT as a preferred second-line option in appropriately selected patients and highlight the importance of treatment sequencing in optimizing long-term outcomes. In keeping with real-world EHR based database limitations, robust subgroup analyses could not be performed based on tumor site and grade owing to heterogeneous ICD coding practices. Further investigation incorporating more granular data is warranted. Adverse events in each cohort. Adverse Event PX P2 Hazard Ratio (95% CI) p value Neutropenia 6.2% 1.9% 3.26 (1.95–5.45) 0.54 Acute Kidney Injury 14.8% 8.3% 1.82 (1.39–2.39) 0.008 Elevated Liver Enzymes 2.0% 1.1% 1.81 (0.87–3.79) 0.40 Thrombocytopenia 18.9% 6.9% 2.90 (2.19–3.82) 0.66 Anemia 35.2% 24.3% 1.55 (1.32–1.83) 0.59
Abhyankar et al. (Thu,) studied this question.