Evolution of Radioligand Therapy in NETs

Dr. Aman Chauhan introduces the program on radioligand equivalents and the 505(b)(2) pathway in neuroendocrine tumor (NET) treatment, joined by Dr. Andrew Hendifar, Dr. Heloisa Soares (medical director of the theranostics program at University of Utah), and Dr. Ghassan El-Haddad (vice chair for radiopharmaceutical and nuclear oncology at Moffitt Cancer Center, nuclear medicine physician and interventional radiologist).

Dr. Hendifar describes the transformative evolution of radioligand therapy in NETs. Before approval in the United States, patients with functional NETs had limited options beyond somatostatin analog (SSA) therapy (titrating doses and discussing cytoreduction), whereas some patients traveled to Europe to access peptide receptor radionuclide therapy (PRRT) that had been used there for decades. The NETTER-1 trial led to FDA approval of lutetium-177 (¹⁷⁷Lu) dotatate, enabling multidisciplinary program development across centers nationally and catalyzing a groundswell of research. Approval was granted for all gastroenteropancreatic NETs (GEP-NETs), building on European data submitted with the application, even though the pivotal study enrolled midgut patients. Subsequent data have supported first-line use in select populations, retreatment strategies, and expanding indications.

Dr. El-Haddad, a NETTER-1 study author, reflects on the unexpected magnitude of the radiopharmaceutical explosion that followed, noting that his prior experience with liver-directed therapies highlighted how limited patient options had been. He now anticipates ongoing expansion including potential re-treatment and next-generation PRRT options.

Dr. Soares describes the rapidly expanding application of radioligand therapy beyond NETs, with phase 1, 2, and phase 3 trials underway in prostate cancer, breast cancer, glioblastoma, pancreatic cancer, lung cancer, and sarcoma, and the anticipated further frontier of combination strategies with immunotherapy and chemotherapy.