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

Abstract

Background 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.

Use and perceived utility of [18F]FDG PET/CT in neuroendocrine neoplasms: A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022

“…A recent study analysing data collected in a Spanish national database, including patients treated with at least one PRRT cycle, reported that FDG PET/CT was not performed before PRRT in approximately 70% of cases. 22 When performed, FDG PET/CT was discordant with SST PET/CT in 17% of cases and concordant in approximately 10%. 22 The respondents were in favour of the use of FDG in NET G3 before curative surgery, and in NEC before curative intended surgery, underlying the role of metabolic imaging to exclude the presence of distant metastasis that might force a change of treatment strategy.…”

“…22 When performed, FDG PET/CT was discordant with SST PET/CT in 17% of cases and concordant in approximately 10%. 22 The respondents were in favour of the use of FDG in NET G3 before curative surgery, and in NEC before curative intended surgery, underlying the role of metabolic imaging to exclude the presence of distant metastasis that might force a change of treatment strategy. In clinical practice, high-grade NEN, especially if metastatic, are often studied with diagnostic CT and/or MRI alone, as it is generally sufficiently precise when metastatic disease is present and palliative treatment is about to be initiated.…”

“…Notwithstanding the above‐mentioned data, FDG PET/CT is still not part of the routine pre‐PRRT assessment in many centres and is not routinely included in most on‐going PRRT trials. A recent study analysing data collected in a Spanish national database, including patients treated with at least one PRRT cycle, reported that FDG PET/CT was not performed before PRRT in approximately 70% of cases 22 . When performed, FDG PET/CT was discordant with SST PET/CT in 17% of cases and concordant in approximately 10% 22 …”

Safety and efficacy of peptide receptor radionuclide therapy in patients with advanced pheochromocytoma and paraganglioma: A single‐institution experience and review of the literature

“…13 studies reported median PFS. This was not reached in three studies 22,24,25 and was 30.3 months (range 17–39 months) in the remaining 10 studies 7 . The median OS was not reached in six studies 7,9,13,20,24,28 and was 60.8 months (range 44–142.6 months) in the remaining five studies 15,17,19,25,28 …”

“…This was not reached in three studies 22,24,25 and was 30.3 months (range 17-39 months) in the remaining 10 studies. 7 The median OS was not reached in six studies 7,9,13,20,24,28…”