177Lu-DOTA0-Tyr3-Octreotate vs. Octreotide LAR in Somatostatin Receptor Positive Tumours

The principal examination of the phase 3 NETTER-1 clinical trial demonstrated notable enhancement in progression-free survival when administering ¹⁷⁷Lu-Dotatate in combination with long-acting octreotide, compared to high-dose long-acting octreotide alone, for individuals with advanced midgut neuroendocrine tumors. The investigators presented the pre-planned ultimate assessment of the general survival and long-standing safety outcomes. It was an open-label, randomized manner and included patients from 41 sites in eight countries spanning Europe and the USA. The inclusion criteria for this study were patients aged 18 years or older who had locally advanced or metastatic, well-differentiated midgut neuroendocrine tumors that were positive for somatostatin receptors. Patients were required to have a Karnofsky performance status score of 60 or higher and to have experienced disease progression while on a fixed-dose long-acting octreotide regimen.

The subjects were randomly allocated (1:1) through an interactive web-based response system to receive intravenous ¹⁷⁷Lu-Dotatate 7·4 GBq (200 mCi) every 8 weeks (four cycles) in combination with intramuscular long-acting octreotide 30 mg ( ¹⁷⁷Lu-Dotatate group) or high-dose long-acting octreotide 60 mg every 4 weeks (control group). The presentation of the significant secondary endpoint of overall survival in the intention-to-treat population has followed up the previously documented primary endpoint of progression-free survival. The ultimate survival assessment was predetermined to occur upon either 158 fatalities or 5 years after randomizing the last patient, whichever occurred first. Throughout the extended monitoring period, the cohort receiving ¹⁷⁷Lu-Dotatate exclusively exhibited adverse events of particular concern.

Between September 6th, 2012, and January 14th, 2016, 231 patients were enrolled and subjected to random assignment for treatment. The final analysis, as predetermined, was conducted at the end of 5 years after random patient assignment, during which 142 deaths were observed. The median follow-up period was 76.3 months (with a range of 0.4-95.0 months) for the group treated with ¹⁷⁷Lu-Dotatate and 76.5 months (with a range of 0.1-92.3 months) for the control group. The secondary endpoint about overall survival did not meet the criteria. The median overall survival was observed to be 48.0 months (95% CI 37.4-55.2) in the ¹⁷⁷Lu-Dotatate group and 36.3 months (25.9-51.7) in the control group (HR 0.84 [95% CI 0.60-1.17]; two-sided P=0.30). Three (3%) out of 111 patients in the ¹⁷⁷Lu-Dotatate cohort experienced grade 3 or higher treatment-related serious adverse events throughout the extended monitoring period. However, no additional treatment-related serious adverse events were documented following the safety analysis cutoff. Of the 111 patients who received ¹⁷⁷Lu-Dotatate, 2% developed myelodysplastic syndrome. Among these patients, one individual passed away 33 months after randomization, the solely reported death related to ¹⁷⁷Lu-Dotatate treatment. No myelodysplastic syndrome or acute myeloid leukemia incidences were reported during extended observation periods.

Source:https://pubmed.ncbi.nlm.nih.gov/34793718/

Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT01578239

Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP; NETTER-1 investigators. ¹⁷⁷Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumors (NETTER-1): final overall survival and long-term safety results from an open-label, randomized, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-1763. doi: 10.1016/S1470-2045(21)00572-6. Epub 2021 Nov 15. Erratum in: Lancet Oncol. 2022 Feb;23(2):e59. PMID: 34793718.