NETTER-2 Trial: Lutathera Cuts Risk of Death by 72% in Neuroendocrine Tumor Treatment

Novartis announced groundbreaking results from the NETTER-2 trial, showing Lutathera plus octreotide LAR significantly reduces the risk of death by 72% in patients with advanced GEP neuroendocrine tumors. This first successful Phase III trial of radioligand therapy (RLT) in a first-line setting marks a major advancement in cancer treatment.

In a landmark development for cancer therapy, the Phase III NETTER-2 trial, led by Novartis, demonstrated that Lutathera® plus octreotide LAR significantly extends median progression-free survival to 22.8 months and reduces disease progression or death by 72% in advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The study's findings, presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium, mark the first successful use of radioligand therapy (RLT) as a first-line treatment.

Jeff Legos, Global Head of Oncology Development at Novartis, highlighted broader implications of these results. He pointed, “This is the first positive Phase III trial of a radioligand therapy in first-line setting, and overall efficacy and safety results are amongst the most clinically relevant observed to date in this kind of advanced cancer, addressing a significant unmet need for patients with newly diagnosed advanced GEP-NETs.”

The trial focused on the efficacy of Lutathera® (lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) in combination with long-acting release (LAR) octreotide, marking a significant stride in first-line treatments for this cancer type.

One of the key metrics in the trial was the progression-free survival (PFS). Patients treated with Lutathera® and octreotide LAR experienced a median PFS of 22.8 months, a significant improvement over the 8.5 months observed with high-dose octreotide LAR. Moreover, the objective response rate (ORR) was notably higher in the Lutathera® group, marking a substantial advancement in treating this life-threatening cancer.

Dr. Simron Singh, an associate professor at the University of Toronto, emphasized the transformative nature of these results and stated, “These positive results for Lutathera are practice-changing and offer new first-line treatment data for patients who have a significant unmet need. This study confirms the clinical benefit of first-line radioligand therapy for newly diagnosed patients living with these types of advanced GEP-NETs.

Safety is a paramount concern in any clinical trial. In the NETTER-2 study, no unexpected safety issues were noted, and the findings align with Lutathera®'s established safety profile. Most participants in the Lutathera® group completed the full treatment course, and the most common adverse events were manageable and in line with expectations.

GEP-NETs, originating in neuroendocrine cells, are often considered slow-growing cancers. However, some can progress rapidly and have a poor prognosis, especially when diagnosis occurs at advanced stages. Given the increasing incidence of NETs, continued research and development in treatment options are crucial.

The NETTER-2 trial, ongoing for further evaluation of secondary endpoints, including overall survival and long-term safety, represents a beacon of hope for those battling advanced GEP-NETs. It underscores Novartis' commitment to pioneering treatments in the realm of RLT and reimagining cancer care for patients worldwide.