Efficacy and safety of peptide radionuclide therapy with ¹⁷⁷Lu-DOTATATE in Japanese patients with advanced neuroendocrine neoplasm: a multicenter retrospective study (JON2203-N)

Background: Peptide receptor radionuclide therapy (PRRT) is an effective treatment for neuroendocrine neoplasms (NENs); however, real-world data in Asia remain limited. Methods: In this multicenter, nationwide study, we retrospectively analyzed 422 patients with unresectable or recurrent NENs who received ¹⁷⁷Lu-DOTATATE-based PRRT at 33 institutions in Japan. Safety analyses were conducted in all enrolled patients and efficacy in 383 patients with complete covariates. Results: The median age was 64 years. The most common primary sites were pancreas (n = 210, 54.8%) and hindgut (n = 81, 21.1%), with fewer midgut cases (n = 19, 5.0%). The tumor grades were G1 (13.3%), G2 (71.2%), G3 (14.6%), and neuroendocrine carcinoma (1.8%). The objective response rate (ORR) was 37.6%, favorable in pancreas (45.2%) and hindgut (40.7%). The median progression-free survival (PFS) was 21.4 months (95% confidence interval [CI], 19.7–22.8). Of 24 patients with hormonal symptoms, 18 (75%) showed marked improvement. Multivariate analysis revealed the following predictors: for ORR (odds ratio, 95% CI), pancreas (4.02, 2.18–7.78), hindgut (3.14, 1.53–6.69), Krenning score (KS) of 4 (2.96, 1.54–6.04), and liver metastasis ≤ 30 mm (1.64, 1.01–2.67); for PFS (hazard ratio, 95% CI), Ki-67 < 10% (0.46, 0.32–0.66), KS of 4 (0.65, 0.43–0.99), liver tumor burden < 50% (0.59, 0.39–0.89), liver tumor size ≤ 30 mm (0.49, 0.32–0.74), and combination with somatostatin analogs (0.64, 0.42–0.99). Grade ≥ 3 adverse events were infrequent, including hematologic (18%) and renal toxicities (< 1%). Conclusions: ¹⁷⁷Lu-DOTATATE demonstrated favorable efficacy and safety in Japanese patients, particularly for pancreatic and hindgut NENs, with symptomatic benefits in functional tumors.