They are rare, and arise from cells spread throughout the body, which is why they can affect different organs, and their incidence has increased in recent decades. We are talking about neuroendocrine tumors (NETs): in most cases they are slow growing, but some can progress quickly and for this reason they are often diagnosed when they are already in an advanced stage, for which few therapeutic possibilities exist today. However, new hope comes from radioligands for a particular type of neuroendocrine tumors, gastroenteropancreatic tumors (GEP-NET). The latest results from the Netter-2 study show that 177lutetium oxodotreotide in addition to the first-line drug octreotide extended release (LAR) reduced the risk of disease progression or death by 72% compared to high-dose LAR alone . The study concerned, in particular, patients with well-differentiated, grade 2/3, somatostatin receptor positive (SSTR+) GEP-NETs. The data was presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium 2024.
Therapy with 177lutetium oxodotreotide
“The positive results of 177lutetium oxodotreotide are able to change clinical practice by offering patients an answer to an unmet clinical need through new evidence in first-line treatment – he comments Salvatore Tafuto, Director of the Sarcoma and Rare Tumors Complex Structure at the RCCS National Cancer Institute ‘Fondazione G. Pascale’ in Naples and coordinator of the NETTER-2 study at national level – This study confirms the first-line clinical benefit of radioligand therapy in patients with new diagnosis of advanced GEP-NET. The strength of the study was also able to demonstrate that this innovative approach not only improves patients’ progression-free survival and clinical response, with a reduction in disease diameters, and therefore tumor burden, but is well tolerated, also allowing excellent quality of life for patients. Many patients continued their working and relationship lives without problems, with little short-term side effects. Such results help give doctors confidence in using 177lutetium oxodotreotide as a first-line treatment in patients with this potentially lethal cancer.”
The NETTER-2 study is ongoing to evaluate overall survival and long-term safety. To date, no new or unexpected safety findings have been observed and the data are consistent with the already established safety profile of 177lutetium oxodotreotide. Most patients (88%) in the experimental arm received four cycles of treatment; the most common adverse events were nausea (27.2% vs 17.8%), diarrhea (25.9% vs 34.2%) and abdominal pain (17.7% vs 27.4%), while the most common adverse event grade ≥3 was decreased lymphocyte count (5.4% vs 0%).
How radioligands work
But what are radioligands? “Radioligand therapy acts like internal radiotherapy aimed at the tumor – explains Secondo Lastoria, Director of the Nuclear Medicine and Radiometabolic Therapy Complex Structure at the RCCS National Cancer Institute ‘Fondazione G. Pascale’ in Naples -. The ligand recognizes and binds specifically to the receptors expressed on tumor cells, and a radioisotope carries out the therapeutic action, releasing radiation that damages the DNA. This approach has unprecedented specificity and sensitivity, which is also why radioligand therapy can be considered an important paradigm of personalized medicine.”
by Tiziana Moriconi
The clinical experience on radioligands derives precisely from the treatment of neuroendocrine tumors. “This is the first positive Phase III study of a first-line radioligand therapy, and the overall efficacy and safety results are among the most clinically relevant seen to date in this type of advanced cancer, meeting a high need clinical dissatisfaction for patients newly diagnosed with advanced GEP-NET – concludes Jeff Legos, Global Head of Oncology Development at Novartis. “The positive results represent a significant progress and further confirm our strategy of research and development of radioligand therapy in early therapeutic lines or in different stages of disease, to improve patient outcomes”.