First-line therapy with lutetium (Lu)-177 dotatate may improve progression-free survival (PFS) and objective response rates in patients with high-grade gastroenteropancreatic neuroendocrine tumors—potentially establishing a new standard of care, according to a press release from ASCO. The research was presented by Singh et al at the 2024 ASCO Gastrointestinal Cancers Symposium (Abstract LBA588). In the phase III NETTER-2 trial, researchers randomly assigned 226 patients newly diagnosed with somatostatin receptor–positive high grade 2 or 3 advanced gastroenteropancreatic neuroendocrine tumors to receive either four cycles of Lu-177 dotatate plus 30 mg of octreotide long-acting release at 8-week intervals (n = 151) or 60 mg of octreotide alone every 4 weeks (n = 75). The researchers noted that 35% of the patients had grade 3 tumors, and 54.4% and 29.2% of the tumors were located in the pancreas and small intestine, respectively. The primary endpoint of the trial was PFS, and the secondary endpoint was objective response rate. Compared with those who received octreotide alone, the researchers found that the patients who received Lu-177 dotatate plus octreotide experienced extended median PFS (22.8 months vs 8.5 months, respectively) and higher overall response rates (43.0% vs 9.3%). The patients in the combination treatment arm had a 72.4% reduction in the risk of disease progression. Adverse events in the combination arm included grade 3 or 4 leukopenia, anemia, and thrombocytopenia—each affecting fewer than three of the patients—and one case of myelodysplastic syndrome. The study authors concluded: “Our study showed significant PFS and unprecedented response rates, offering a new, safe treatment option in a field with no established standard of care.”