Safety and response after peptide receptor radionuclide therapy with 177Lu‐DOTATATE for neuroendocrine tumors in phase 1/2 prospective Japanese trial

Background The present prospective phase 1/2 study aimed to elucidate the efficacy and safety of 177Lu‐DOTATATE (four cycles of 7.4 GBq) in Japanese patients with unresectable, progressive neuroendocrine tumors (NETs). Methods From April 2018 to October 2020, 15 patients with advanced NETs (five midgut, eight pancreatic, and two lung NETs) were enrolled. Objective response rate (ORR), progression‐free survival (PFS), and adverse events (AEs) were evaluated. Pharmacokinetics and dosimetry were also evaluated in three midgut patients. Results The mean absorbed doses of 177Lu‐DOTATATE to the kidneys (20.7 Gy/29.6 GBq) and the bone marrow (0.631 Gy/29.6 GBq) were within the radiation tolerance doses. The ORR of the whole population was 53% (90% CI, 30%‐76%). ORRs of the midgut and non‐midgut NETs were 60% (90% CI, 19%‐92%) and 50% (90% CI, 22%‐78%), respectively. There was no difference in the maximum reduction rate of the sum of the target lesion diameters between patients with midgut and non‐midgut NET. The median PFS was not reached; the PFS rate at 52 weeks was 80% (90% CI, 56.1%‐91.7%). AEs of Grade 3 or higher were lymphopenia (47%) and leukopenia (7%). Conclusion 177Lu‐DOTATATE demonstrated remarkable tumor shrinkage and tolerability in Japanese patients with advanced NETs. This study is the first clinical trial of 177Lu‐DOTATATE in Japan, providing the pharmacokinetics and dosimetry of Japanese patients with midgut neuroendocrine tumors. Kudo and colleagues elucidated that 177Lu‐DOTATATE therapy for midgut and non‐midgut neuroendocrine tumors had higher objective response rates than in previous reports, with similar adverse event rates.