177Lu-Dotatate Provides Clinically Relevant But Non-Significant OS Advantage for Midgut NETs

Patients with advanced midgut neuroendocrine tumors experienced a clinically relevant improvement in median overall survival when treated with 177Lu-Dotatate compared to the high-dose long-acting octreotide control group, although the difference is not significant.

Although it did not significantly improve median overall survival (OS) in patients with advanced neuroendocrine tumors of the midgut, treatment with 177Lu-Dotatate (Lutathera) Provided Potential Clinically Relevant Improvement Over Control, Long-Acting High-Dose Octreotide (Sandostatin), According to Results from the Phase 3 NETTER1 Trial (NCT01578239) Published in Lancet Oncology.

Although the secondary OS endpoint was not met, the median OS was 48.0 months (95% CI, 37.4-55.2) in the 177Lu-Dotatate group at a median follow-up of 76.3 months compared and 36.3 months (95% CI, 25.9-51.7) in the control group at a median follow-up of 76.5 months (HR, 0 .84, 95% CI, 0.60-1.17; P = .30).

“The final analysis of the NETTER1 study showed that treatment with 177LuDotatate did not significantly improve overall survival compared to high-dose long-acting octreotide; however, a presumably clinically relevant difference in median overall survival of 11.7 months with 177Lu-Dotatate has been registered with a favorable long-term safety profile in patients with advanced, progressive, well-differentiated, grade 1 and grade 2 midgut neuroendocrine tumors,” wrote the researchers.

Eligible patients were 18 years of age or older and had advanced, well-differentiated midgut neuroendocrine tumors with positive uptake on 111InDTPAoctreotide scintigraphy on all target lesions. Patients also had confirmed disease progression according to RECIST 1.1 criteria.

Patients were randomized 1:1 to receive 177Lu-Dotatate 7.4 GBq intravenously every 8 weeks for 4 cycles plus concomitant long-acting octreotide 30 mg given intramuscularly, or high-dose long-acting octreotide 60 mg given intramuscularly every 4 weeks.

The primary endpoint of the NETTER-1 study was progression-free survival, which has been previously reported.

A total of 101 patients in the 177The Lu-Dotatate group and 99 patients in the control group were followed up long term. Annual survival rates for 177The LuDotatate and control groups, respectively, were 91.0% (95% CI, 84.0%-95.1%) and 79.7% (95% CI, 70.8%-86.1% ) at 1 year; 76.0% (95% CI, 66.7%-83.0%) and 62.7% (95% CI, 52.6%-71.2%) at 2 years; 61.4% (95% CI, 51.4%-69.9%) and 50.1% (95% CI, 40.0%-59.4%) at 3 years; 49.5% (95% CI, 39.5%-58.6%) and 41.8% (95% CI, 31.8%-51.4%) at 4 years; and 37.1% (95% CI, 27.8%-46.4%) and 35.4% (95% CI, 25.7%-45.2%) at 5 years.

Six percent of patients in 177The Lu-Dotatate group experienced serious treatment-emergent adverse events (TRAE) of Grade 3 or higher throughout the study. During long-term follow-up, 3% of patients experienced serious AEs. Only one patient died from grade 5 myelodysplastic syndrome and another patient presented with grade 3 respiratory infection and refractory cytopenia with multilineage dysplasia leading to treatment discontinuation. After the closure of the safety analysis, no new serious EITRs were reported.

“These results highlight the difficulties in demonstrating a [OS] benefit in patients with advanced, well-differentiated neuroendocrine tumors, considering the prolonged survival in this indolent tumor type, the heterogeneity of previous treatments, the potential for crossover within the trial, and the availability of other additional treatment options,” the researchers concluded.


Strosberg JR, Caplin ME, Kunz PL, et al. 177Lu-Dotatate Plus Long-Acting Octreotide Versus High-Dose Long-Acting Octreotide in Patients With Midgut Neuroendocrine Tumors (NETTER-1): Overall Survival and Long-Term Safety Final Results from an Open-Label Trial , randomized, controlled phase 3 . Lancet Oncol. 2021;22(12):1752-1763. doi:10.1016/S1470-2045(21)00572-6

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