Long‐term survival and toxicity in patients with neuroendocrine tumors treated with 177Lu‐octreotate peptide radionuclide therapy

Background Peptide receptor radionuclide therapy (PRRT) has shown favorable results in neuroendocrine tumors (NETs). Long‐term safety and efficacy data for 177Lu‐octreotate PRRT, particularly in combination with chemotherapy, is lacking. Methods The authors conducted a retrospective review of the long‐term toxicity and survival outcomes of 104 patients with advanced NETs treated on 4 phase 2 clinical trials with Lutetium‐177‐octreotate (177Lu‐octreotate) PRRT, mostly in combination with chemotherapy. Median follow‐up was 68 months, which represents the longest follow‐up study of 177Lu‐octreotate PRRT for NETs to date. Results Median progression‐free survival (PFS) was 37 months, and median overall survival (OS) was 71 months. Five‐ and 10‐year OS were 62% and 29%, and 5‐ and 10‐year PFS were 36% and 21%, respectively, demonstrating 177Lu‐octreotate can provide durable responses. PRRT was well tolerated with 1.9% of patients developing chronic renal impairment and 1% of patients developing long‐term thrombocytopenia. Interestingly, there was a relatively high rate of myelodysplasia (MDS)/leukemia (6.7%), possibly attributable to the longer follow‐up (with all except 1 case occurring more than 4 years after PRRT treatment) or to the addition of concurrent chemotherapy. Conclusions Lutetium‐177‐Octreotate PRRT remains an efficacious and well tolerated treatment in long‐term follow‐up. For clinicians deciding on the timing of PRRT for individual patients, the 6.7% long‐term risk of MDS/leukemia needs to be balanced against the 21% PFS at 10 years. Lutetium‐177‐octreotate peptide receptor radionuclide therapy is a safe and efficacious treatment for advanced neuroendocrine tumors. In long‐term follow‐up, in combination with radio‐sensitizing chemotherapy, the long‐term risk of myelodysplasia and leukemia appears to be greater than previously appreciated.