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. 2023 Jul;50(8):2486-2500.
doi: 10.1007/s00259-023-06166-8. Epub 2023 Mar 6.

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

Mercedes Mitjavila  1 , Paula Jimenez-Fonseca  2 , Pilar Belló  3 , Virginia Pubul  4 , Juan Carlos Percovich  5 , Amparo Garcia-Burillo  6 , Jorge Hernando  7 , Javier Arbizu  8 , Emilia Rodeño  9 , Montserrat Estorch  10 , Belén Llana  11 , Maribel Castellón  12 , Lina García-Cañamaque  13 , Pablo Gajate  14 , Maria Carmen Riesco  15 , Maria Begoña Miguel  16 , David Balaguer-Muñoz  17 , Ana Custodio  18 , Juana María Cano  19 , Alexandra Repetto  20 , Pilar Garcia-Alonso  21 , Maria Angustias Muros  22 , Jose Luis Vercher-Conejero  23 , Alberto Carmona-Bayonas  24
Affiliations

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

Mercedes Mitjavila et al. Eur J Nucl Med Mol Imaging. 2023 Jul.

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.

Keywords: Lung; Lutathera; Neuroendocrine tumor; PRRT; Radionuclide therapy; [177Lu]Lu-DOTATATE.

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Conflict of interest statement

ACB has received travel grants and participated in advisory boards from Novartis. The other authors declare that they have no conflicts of interest in relation to the scope of this work. This is an academic study.

Figures

Fig. 1
Fig. 1
Response rate, assessed with anatomical imaging (A), SSR imaging (B), clinical interview (C), and with markers (D). Bivariate χ2 tests of response and tumor type, with SSR imaging: χ2 = 15.33, degrees of freedom [d.f.] = 15, p value = 0.4277; anatomical: χ2 = 29.33, d.f. = 20, p value = 0.0816; clinical: χ2 = 15.64, d.f. = 15, p value = 0.4047; and biomarkers: χ2 = 13.86, d.f. = 15, p value = 0.5359
Fig. 2
Fig. 2
Kaplan-Meier curves for progression-free survival (A) and overall survival (B) based on tumor site. N/n sample size/events, PFS progression-free survival, CI confidence interval, NR not reached, PPGL pheochromocytoma and paraganglioma, GEP gastroenteropancreatic, NGEP non-gastroenteropancreatic, BP bronchopulmonary
Fig. 3
Fig. 3
Swimmer plot with results of responses and survival in individual tumors. Each bar represents one patient. PRRT peptide receptor radionuclide therapy, PPGL pheochromocytoma/paraganglioma, GEP gastroenteropancreatic
See this image and copyright information in PMC

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