According to primary analysis results from the phase 3 NETTER-2 study, first-line [177Lu] Lu-DOTA-TATE (¹⁷⁷Lu-DOTATATE), a radioligand therapy, significantly prolonged progression-free survival (PFS) and demonstrated a clinically meaningful objective response rate (ORR) among patients with newly diagnosed, advanced grade 2 and 3 gastroenteropancreatic neuroendocrine tumors. 

These results were presented by lead author Simron Singh, MD, MPH, Sunnybrook Odette Cancer Center, University of Toronto, Ontario, Canada, at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, California.

In this study, 226 patients diagnosed with somatostatin receptor-positive high, grade 2/3 advanced gastroenteropancreatic neuroendocrine tumors within 6 months of trial enrollment were randomized on a 2-to-1 basis to receive either 4 cycles of ¹⁷⁷Lu-DOTATATE (4 × 7.4 GBq) plus 8-weekly intervals of octreotide long-acting release (30 mg) followed by octreotide every 4 weeks (¹⁷⁷Lu-DOTATATE arm; n = 151) or octreotide long-acting release (60 mg) every 4 weeks (control arm; n = 75). The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR) and safety. 

At analysis, median PFS was prolonged by approximately 14.3 months, from 8.5 months in the control arm to 22.8 months in the ¹⁷⁷Lu-DOTATATE arm (stratified hazard ratio [HR], 0.276; 95% confidence interval [CI], 0.182 to 0.418; P < .0001). ORR was 43% in the ¹⁷⁷Lu-DOTATATE arm and 9.3% in the control arm (stratified odds ratio, 7.81; 95% CI, 3.32 to 18.4; P < .0001). Grade 3/4 adverse events occurring in ≤3 patients included leukopenia, anemia, and thrombocytopenia. One case of myelodysplastic syndrome was reported.

“This is the first randomized study to demonstrate efficacy of [radioligand therapy as first-line] treatment in any malignancy and will change clinical practice,” stated Dr Singh and coauthors. “Further investigations of [radioligand therapy] as a therapeutic option in other settings is warranted.”

Source:

Singh S, Halperin DM, Myrehaug S, et al. [177Lu] Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study. Presented at the 2024 ASCO Gastrointestinal Cancer Symposium; January 18-20, 2024; San Francisco, California. Abstract LBA588