A Promising First-Line Treatment for Neuroendocrine Tumors

The ¹⁷⁷Lutetium radiolabeled somatostatin analogue ¹⁷⁷Lu-Dotatate is approved for the later-line treatment of advanced somatostatin receptor–positive grade 1 or 2 midgut neuroendocrine tumors (NETs) progressing on somatostatin analogue therapy. Limited data are available regarding optimal first-line treatment of well-differentiated higher grade 2 and 3 gastroenteropancreatic (GEP) somatostatin receptor–positive NETs.

Investigators now report results of the NETTER-2 trial evaluating first-line therapy in somatostatin receptor–positive grade 2 and 3 well-differentiated GEP NETs. In the industry-sponsored, open-label, phase 3 trial, patients were randomized to treatment with ¹⁷⁷Lu-Dotatate combined with octreotide long-acting repeatable (LAR; 30 mg every 8 weeks) or octreotide LAR alone (60 mg every 4 weeks). Of the 226 patients, 54% had pancreatic and 29% had small-intestinal primary tumors; 65% had grade 2 and 35% had grade 3 NETS; 90% had hepatic and 60% had lymph node metastases.

The primary endpoint of progression-free survival was superior with ¹⁷⁷Lu-Dotatate plus octreotide LAR compared with octreotide LAR alone (median, 22.8 vs. 8.5 months; hazard ratio, 0.276; P<0.0001). Response rate also was superior with ¹⁷⁷Lu-Dotatate plus octreotide LAR over octreotide LAR alone (43% vs. 9.3%; odds ratio, 7.81; P<0.0001). Time to deterioration in quality of life did not differ between groups. Overall survival (OS) results are pending. One case of myelodysplastic syndrome occurred in the ¹⁷⁷Lu-Dotatate arm, but no new safety signals were observed.