SURVIVAL OUTCOMES FOR GASTROENTERO-PANCREATIC NEUROENDOCRINE TUMORS PATIENTS TREATED WITH 177LU-DOTATATE IN A BRAZILIAN REFERENCE CENTER: A SIX-YEAR FOLLOW-UP EXPERIENCE

Introduction: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common NETs primary site. Lutetium-177-DOTATATE (Lu-177) is the standard treatment for patients with grade 1 (G1) or grade 2 (G2) midgut NETs who had disease progression during first-line somatostatin analogue therapy. Objective: Retrospectively evaluate the epidemiological profile, histopathological features, and survival outcomes of patients with GEP-NETs who received treatment with Lu-177 at our institution. Methods: We performed a retrospective chart review including all-grade advanced GEP-NETs treated with at least one Lu-177 dose. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan–Meier method, considering the interval from the first Lu-177 dose to the last appointment. Cox regression analysis was performed for PFS adjusted by grade, primary tumor site, metastasis sites (1 versus 2 or more), presence of liver metastasis, and previous local or systemic treatments. Results: 36 patients were included; their median age was 51 (33-80). 19 (52.8%) patients had primary pancreatic tumors, and 17 (47.2%) were non-pancreatic. Of all samples, 10 (28.6%) were classified based on Ki67% as G1, 18 (51.4%) as G2, and 7 (20%) as G3. After a median follow-up of 90.5 months (16-122), only 4 (11.1%) patients died (n=3 G3, n=1 G2) and 58,3% of patients are still on follow-up. Survival rates were 92,7% (95% CI 73.7 – 98.1) at 24 months and 86,9% (95% CI 63.5 – 95.7) at 36 months. The median OS was not reached for G1 and G2 tumors and was 30 months for G3 tumors (p=0.001). Of the 34 patients eligible for PFS analysis, the median was 23 months (95% CI 30.5-64.9). G3 tumors were associated with lower PFS in the univariate and multivariate analysis compared to G1 [7 versus 30 months; HR 8.41 (95%CI 2.2-31.0;p=0.001)]. In multivariate analyses, primary site, metastasis sites, number of previous systemic treatments, and presence of secondary liver lesions did not reach statistical correlation with PFS. Those who did not receive previous local treatments exhibited a trend toward PFS benefit (p=0.117). Lu-177 was well tolerated; 12 (33.3%) patients disclosed toxicity, with the most frequent being fatigue (n=4). No grade 3 or 4 toxicities were reported. Conclusion: Our real-life data supports that Lu-177 is a feasible and safe option for patients with G3 and pancreatic NETs, who are underrepresented in available randomized clinical trials in the literature.