Lu-177 Dotatate PRRT is an established and expanding treatment for metastatic GEP-NETs

Patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) often face limited treatment options upon progression, especially in metastatic settings. While somatostatin analogs are a first-line therapy, disease progression necessitates alternative strategies. Peptide Receptor Radionuclide Therapy (PRRT), specifically with Lu-177 Dotatate, targets somatostatin receptors highly expressed on these tumor cells, delivering localized radiation. This approach offers a distinct mechanism compared to conventional chemotherapy or targeted therapies, addressing a critical gap in managing advanced, progressive GEP-NETs.

This comprehensive review synthesized existing evidence regarding Peptide Receptor Radionuclide Therapy (PRRT) with Lu-177 Dotatate in metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The authors systematically analyzed data from pivotal clinical trials, including NETTER-1 and NETTER-2, which established PRRT's role in second-line treatment. They also evaluated emerging comparative and combination studies, exploring PRRT's potential in first-line settings, higher-grade disease, retreatment strategies, and special patient populations. The review further considered novel approaches, such as alpha-emitting radionuclides and somatostatin receptor antagonists, to provide a holistic view of the evolving therapeutic landscape for GEP-NETs.

The review confirmed Lu-177 Dotatate PRRT as an established second-line treatment for progressive GEP-NETs following somatostatin analog failure. Evidence from trials like NETTER-1 and NETTER-2 demonstrated significant improvements in progression-free survival and objective response rates. Indications are expanding into first-line treatment and higher-grade disease settings. Emerging data suggest a potential role for PRRT alongside targeted therapies and chemotherapy, though optimal sequencing and overall survival benefits require further clarification. Retreatment strategies are also being explored, offering extended benefits for select patients. Novel approaches, including alpha-emitting radionuclides and somatostatin receptor antagonists, are broadening the therapeutic landscape, targeting somatostatin receptors with enhanced potency or different decay characteristics. Ongoing prospective trials are anticipated to refine patient selection and further define PRRT's role across diverse tumor grades and clinical scenarios. This indicates a robust and evolving treatment paradigm.

Lu-177 Dotatate PRRT has demonstrated significant improvements in progression-free survival and objective response rates in metastatic GEP-NETs, establishing its role and expanding its indications.