Real-world 177Lu-DOTATATE peptide receptor radionuclide therapy: Treatment outcomes with dosing variations and in non-midgut neuroendocrine tumors.

Abstract

593 Background: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE has been used for neuroendocrine tumors (NETs) since its approval in the United States based on demonstrated progression-free survival benefit in grade 1-2 midgut NETs. The recommended dosing is 7.4 GBq (200 mCi) every 8 weeks for 4 doses in total. We examined the post-PRRT outcomes with dosing variations and in patients with non-midgut NETs. Methods: The medical records of 108 PRRT-naïve NET patients who received at least one cycle of PRRT at a single academic institution were reviewed. Among the patients with Ki-67 index ≤ 20%, progression-free survival (PFS) and overall survival (OS) were compared between midgut and non-midgut NETs. Among the patients who did not develop disease progression or mortality during the treatment course, PFS and OS were compared based on dosing variations. Dosing variations were defined as "reduced” (50% of 7.4 GBq/cycle), “delayed” (>12 weeks between cycles), or “fewer” (<4 cycles) doses. Kaplan-Meier survival analysis with log-rank test was used for statistical analysis. Results: Median clinical follow-up was 18.7 months, during which disease progression and death occurred in 54 (50%) and 20 (18%) patients, respectively. Among the 98 patients with Ki-67 index ≤ 20%, those with non-midgut tumors (n=55) showed significantly shorter PFS compared to those with midgut tumors (n=43) with the hazard ratio of 2.0 ( P=0.014, median of 15.6 vs. 26.9 mo.). No difference in OS was found between the two groups ( P=0.83). Among the 93 patients who did not develop disease progression or mortality during the course of PRRT, dosing variations were used in 23 patients. The types of dosing variations were “reduced” in 4 (17%) patients, “delayed” in 16 (70%) patients, and “fewer” in 7 (30%) patients. The reasons for dosing variations were hematologic in 9 (39%) patients, hepatic in 2 (9%) patients, renal in 1 (4%) patient, other medical in 3 (13%) patients, functional in 3 (13%) patients, and logistical in 6 (26%) patients. No difference in PFS ( P=0.20) or OS ( P=0.24) was found based on the presence or absence of dosing variations. Conclusions: Patients with non-midgut NETs show approximately twice the rate of disease progression over time following PRRT than those with midgut NETs. Administering reduced, delayed, or fewer doses of PRRT may still offer comparable benefit compared to the recommended dosing.