Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study

Neuroendocrine tumor; Radionuclide therapyTumor neuroendocrí; Teràpia amb radionúclidsTumor neuroendocrino; Terapia con radionúclidosBackground Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282). Results The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7–not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8–28.1) in pancreatic, and 17.6 months (14.4–33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity. Conclusion This study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.The SEPTRALU registry received external funding from Novartis

Position Statement on the Diagnosis, Treatment, and Response Evaluation to Systemic Therapies of Advanced Neuroendocrine Tumors, With a Special Focus on Radioligand Therapy

Neoadjuvant therapy; Peptide receptor radionuclide therapy; ProgressionTeràpia neoadjuvant; Teràpia amb radionúclids del receptor de pèptids; ProgressióTerapia neoadyuvante; Terapia con radionúclidos del receptor de péptidos; ProgresiónBackground The aim of this study was to provide a guidance for the management of neuroendocrine tumors (NETs) in clinical practice. Material and Methods Nominal group and Delphi techniques were used. A steering committee of 8 experts reviewed the current management of NETs, identified controversies and gaps, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a panel of 26 experts, was selected to test agreement with the statements through 2 Delphi rounds. Items were scored on a 4-point Likert scale from 1 = totally agree to 4 = totally disagree. The agreement was considered if ≥75% of answers pertained to Categories 1 and 2 (consensus with the agreement) or Categories 3 and 4 (consensus with the disagreement). Results Overall, 132 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) progression and treatment response criteria; (3) advanced gastro-enteric NETs; (4) advanced pancreatic NETs; (5) advanced NETs in other locations; (6) re-treatment with radioligand therapy (RLT); (7) neoadjuvant therapy. After 2 Delphi rounds, only 4 statements lacked a clear consensus. RLT was not only recommended in the sequencing of different NETs but also as neoadjuvant treatment, while several indications for retreatment with RLT were also established. Conclusion This document sought to pull together the experts’ attitudes when dealing with different clinical scenarios of patients suffering from NETs, with RLT having a specific role where evidence-based data are limited.This project was funded by Advanced Accelerator Applications, a Novartis company