Phase 2 Study Supports Radionuclide Alpha Therapy in Patients With Advanced Neuroendocrine Tumors

New research presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting shows that the targeted radionuclide alpha therapy, ²²⁵Ac-DOTATATE, has long-term anti-tumor effects against advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The authors, led by Chandrasekhar S. Bal, of the Department of Nuclear Medicine and PET at the All India Institute of Medical Science in New Delhi, India, won the SNMMI Abstract of the Year Award.

GEP-NETs are rare cancers that begin in neuroendocrine cells and can appear throughout the gastroinstesinal tract. Many patients with early-stage disease have surgery for tumor resection, but most people are diagnosed with advanced, metastatic disease. Therefore, a need exists for systemic therapy.

The researchers had previously conducted a pilot study with 32 patients showing the potential of ²²⁵Ac-DOTATATE. In this phase 2 study, the researchers expanded the study sample and followed up over a longer term.

The researchers enrolled 83 consecutive patients with GEP-NETs (34 women and 49 men with a mean age of 54 years) from April 2018 to June 2021. Of the total sample, 56 patients had previously received ¹⁷⁷Lu-DOTATATE, and 27 had not. Each patient received systemic ²²⁵Ac-DOTATATE and a renal-protection protocol every 8 weeks. The study examined hematologic, kidney, and liver function tests before and after each cycle. It also tracked tumors with RECIST 1.1 criteria at baseline and after two cycles.

At a median follow-up of 18 months, 24 patients had died (29%). Analysis showed 12- and 24-month overall survival of 85.3% and 67.6%, respectively. Of those who were alive at follow-up, 2 patients (2.7%) achieved complete response, 32 (43.2%) experienced a partial response, 25 (34%) had stable disease, and 15 (20%) had progressive disease. The study found no grade 3/4 hematological, renal, or hepatic toxicities, except 1 patient with grade 3 thrombocytopenia.

“²²⁵Ac-DOTATATE is a promising therapy option that adds a new dimension to the treatment of end-stage GEP-NETs, especially for patients who have tried all other standard therapy options,” Dr. Bal said. “These results warrant a phase 3, randomized, controlled trial to assess the true efficacy of ²²⁵Ac-DOTATATE versus ¹⁷⁷Lu-DOTATATE.”