Real-world efficacy and safety of peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Authors: Abou Jokh Casas Estephany , Martinez Nieves Purificacion , Anido Herranz Urbano , Cabezas Agricola Jose Manuel , Varela Ferreiro Silvia , Carral Maseda Alberto , Fernandez Calvo Ovidio , Mato Mato Jose Antonio , Nogareda Seoane Zulema , Rodriguez Martinez de LLano Sofia , Quindós Varela Maria , Baron Francisco , Rodriguez Fonseca Omar , Cousillas Castiñeira Antia , Muñiz Garcia Gloria , De Matias Leralta Jose Maria , Fernández Catalina Pablo , Cameselle Teijeiro Jose Manuel , Bernardez Beatriz , Pubul Nuñez Virginia 
Published: January 2021

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Background: PRRT with 177Lu-Dotatate (Lutathera) is a radiolabeled somatostatin analog indicated treatment of somatostatin receptor (STTR) positive GEP-NETs. The study aims to establish the efficacy and safety of PRRT in GEP-NETs in a real-world setting. Methods: We conducted an observational, retrospective, multicentric study of 40 patients with GEP-NET treated with PRRT belonging to GGNET (Galician Research Group on Neuroendocrine Tumors) network at Nuclear Medicine Department of Santiago de Compostela University Hospital (Spain). Patients characteristics, overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity data were retrospectively collected and analyzed. Results: Data from 40 patients (pts) treated between 2016 and 2020 were recorded in this study. Median age was 63.5 years (range 41-85) and 55% were male. The baseline ECOG PS 0/1/2 was 15 (37.5%)/16 (40%)/9 (22.5%). Tumor location was intestinal 26 pts (65%), pancreas in 11 pts (27.5%) and unknown origin in 3 pts (7.5%). 25 pts (62.5%) were none functioning. Tumor grade G1/G2/G3 were 17 pts (42.5%)/ 20 pts (50%)/ 3 pts (7.5%), and Ki 67 < 2/3-20/ > 20%/unknown was 11 pts (27.5%)/ 21 pts (52.5%)/ 3 pts (7.5%)/ 5 pts (12.5%), respectively. The most frequent site of metastasis was liver in 32 pts (80%), lymph nodes in 19 pts (47.5%), peritoneum 11 pts (27.5%) and bone 10 pts (25%). Surgery: 22 pts (55%) primary tumor surgery and 8 pts (20%) metastasectomy. Previous systemic treatments included somatostatin analogs (SSA) in 40 pts (100%), everolimus in 26 pts (65%) and sunitnib in 11 pts (27.5%), others 7 pts (17.5%). 34 pts (85%) completed 4 cycles of treatment (6 pts (15%) non-complete due to premature death). 35 pts were evaluable for early response (after 2 cycles of treatment). Early ORR and DCR were 2.8% and 74.2%, respectively. 26 pts were evaluable after finishing treatment (6 pts premature death and 8 pending evaluation). ORR and DCR were 19.2% and 92.3%. With a median follow up of 21 months, 14 pts (35%) had died. Median OS was not reached (NR) and median PFS was 27.2 m (95% CI 16.0-38.4m). Tumor grade G1-2 (p < 0.001), Ki 67 <20% (p = 0.002), primary tumor surgery (p = 0.039) and metastasectomy (p = 0.030) were associated with prolonged PFS. Mild adverse events were most frequent after the 1º doses in 27.5% patients, and medium-term toxicity was present in 25.6%, mainly hematological, G1-G2 25.6%, and G3 5%. Conclusions: 177Lu-Dotatate is a safe and effective treatment for those patients diagnosed with metastatic GEP-NET and positive somatostatin receptors, with an excellent clinical and radiological response. Furthermore, we have identified some predictive factors to OS that should be taken into consideration.