Abstract
PURPOSE: To compare the efficacy and safety of (177)Lu-DOTATATE plus radiosensitizing capecitabine and octreotide long-acting release (LAR) as first-line systemic therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Data of consecutive patients of advanced inoperable or metastatic grade 1 or 2 GEP-NETs treated with first-line (177)Lu-DOTATATE plus radiosensitizing capecitabine or octreotide LAR from September 2012 to December 2019 were collected and analyzed for response, toxicity, and survival outcomes. RESULTS: Seventy-six patients (median age: 53 years; range 14-81 years) with treatment-naïve advanced grade 1 or 2 GEP-NETs were included. Thirty-six patients received a median cumulative dose of 27.3 GBq of (177)Lu-DOTATATE intravenously at 8-12 weeks' intervals along with 1,250 mg/m(2) oral capecitabine on days 0-14 of each cycle of (177)Lu-DOTATATE, whereas 40 patients were administered 30 mg octreotide LAR intramuscularly every 4 weeks. Using response evaluation criteria in solid tumor 1.1, the objective response rate was 38% in the (177)Lu-DOTATATE arm compared with 15% in the octreotide LAR arm (P = .025), whereas the disease control rates were 88% and 67% in (177)Lu-DOTATATE and octreotide LAR arms, respectively (P = .035). The median durations of progression-free survival in the (177)Lu-DOTATATE and octreotide LAR arms were 54 months and 16 months, respectively (P = .017), whereas the median overall survival was not reached and not significantly different across both the arms. Of the treatment-related adverse events, no major difference was observed in the occurrence of grade 3 or 4 toxicities between the two treatment arms. CONCLUSION: First-line systemic (177)Lu-DOTATATE plus radiosensitizing capecitabine achieved better radiologic response and longer progression-free survival compared with octreotide LAR in patients with advanced grade 1 or 2 GEP-NETs. Future randomized controlled trials are, however, required to determine the best treatment sequence for the treatment-naïve patients with advanced GEP-NETs.