Toxicity and Tolerability of (177)Lu-DOTA-TATE PRRT with a Modified Administered Activity Protocol in NETs of Variable Origin – A Phase 2 Registry Study

Background: Peptide receptor radionuclide therapy (PRRT) has been recently approved for advanced, metastatic, or progressive neuroendocrine tumors (NETs). Objective: This study reports the adverse events (AEs) observed with patient-tailored administered activity. Methods: Fifty-two PRRT naive patients were treated with 177Lu-DOTATATE. The administered activity ranges between 2.78 and 5.55 GBq/cycle using the patient's unique characteristics (age, symptoms, blood work, and biomarkers). Results: The protocol was well tolerated with the overwhelming majority of participants being forty-six (88%), completing all 4 induction therapy cycles. The median cumulative administered activity was 19.6 GBq (ranged 3.8-22.3 GBq). A total of 42/52 (81%) reported at least one symptom, and 43/52 (83%) had evidence of biochemical abnormality at enrollment that would meet grade 1 or 2 criteria for AEs. These symptoms only slightly increase with treatment to 50/52 (96%) and 51/52 (98%), respectively. The most common symptoms were mild fatigue (62%), shortness of breath (50%), nausea (44%), abdominal pain (38%), and musculoskeletal pain (37%). The most common biomarker abnormalities were mild anemia (81%), reduced estimated glomerular filtration rate (eGFR) (58%), increased alkaline phosphatase (ALP) (50%), and leukopenia (37%). Of critical importance, no 177Lu-DOTATATE related grade 3 or 4 AEs were observed. Conclusion: Tailoring the administered activity of 177Lu-DOTATATE to the individual patient with a variety of NETs is both safe and well-tolerated. No patient developed severe grade 3 or 4 AEs. Most patients exhibit symptoms or biochemical abnormality before treatment and this only slightly worsens following induction therapy.