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.