Long-term survival and toxicity in patients with neuroendocrine tumors treated with Lu-177-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 Lu-177-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 (Lu-177-octreotate) PRRT, mostly in combination with chemotherapy. Median follow-up was 68 months, which represents the longest follow-up study of Lu-177-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 Lu-177-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.