Background: Neuroendocrine tumors (NET) have an incidence of around 6.98/100k per year. Long-acting somatostatin receptor agonists (SSA) are first-line therapy for non-resectable disease. In January 2018, the United States FDA approved ¹⁷⁷Lu-DOTATATE (PRRT) for second-line therapy in patients with somatostatin receptor-positive GEP-NETs based on the results from NETTER-1 randomized controlled trials. Those trials did not explore frequency of SSA dosing in relation to ¹⁷⁷Lu-DOTATATE and its effects on mPFS. Methods: This is a retrospective observational analysis of the safety and efficacy of ¹⁷⁷Lu-DOTATATE in treating NETs which progressed on SSA or other second-line therapy, as well as effects on PFS of differential dosing of SSA between PRRT treatments. Organizational IRB approval was obtained. All patients who received ¹⁷⁷Lu-DOTATATE at Scripps MD Anderson Cancer Center from 1/2018 to 12/2022 were identified and relevant data were abstracted from the EHR. Patients received 200 mCi of PRRT followed by SSA every 8 weeks for 4 doses. Disease progression was defined as development of new metastases or growth in diameter of existing disease on imaging. Some patients chose to receive SSA between doses of PRRT for symptomatic control every 4 weeks, and these patients were stratified in analysis. For both groups, the mPFS was calculated and plotted on a Kaplan-Meier survival curve and p-values were calculated using the log-rank method. Results: Demographics:34 patients completed the 4 PRRT doses at our institution. Demographically, our population was similar to NETTER-1 with regards to age (67 ± 12 years) and time since diagnosis (3 years). We included 5 patients with >5% Ki67 staining on pathology. The most common primary site was pancreas in our study compared to ileum in the RCT. Efficacy: The calculated mPFS in our population was 25.4 months (95% CI 11.6 – 43.4), versus in NETTER-1 mPFS had not been reached for the treatment group at 20 months. In our study there was no statistically significant difference in mPFS in patients who had received SSA every 4 weeks versus every 8 weeks (p=0.47). Safety: Symptom-focused side-effects of ¹⁷⁷Lu-DOTATATE were not recorded at our center. Only 2 patients were incompletely treated due to measurable toxicities, including a grade 2 thrombocytopenia, and one patient with a grade 2 leukopenia with grade 3 neutropenia. Conclusions: Our population differed from NETTER-1 not only in size but by including patients with >5% Ki67 staining index which may indicate more aggressive disease. No difference was found in mPFS when dosing patients with SSA every 4 weeks compared to every 8, suggesting that interval SSA treatment for symptomatic control may not interfere with ¹⁷⁷Lu-DOTATATE efficacy. Our analysis suggests that ¹⁷⁷Lu-DOTATATE can be used safely as second-line therapy of NETs at a community-based institution with improved mPFS when compared to the control group studied in the larger NETTER-1 RCT.