Adding ¹⁷⁷Lu-Dotatate to long-acting octreotide did not significantly improve overall survival in patients with advanced midgut neuroendocrine tumors (NET), according to phase 3 results published in The Lancet Oncology.1

However, the addition of ¹⁷⁷Lu-Dotatate did improve the median OS by 11.7 months when compared with high-dose long-acting octreotide alone. Although this difference was not statistically significant, it was deemed clinically relevant by the researchers.

These results come from the final analysis of the phase 3 NETTER-1 trial (ClinicalTrials.gov Identifier: NCT01578239). The trial included 231 patients with locally advanced or metastatic, well differentiated, somatostatin receptor-positive midgut NETs whose disease had progressed on fixed-dose long-acting octreotide.


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The patients were randomly assigned to receive long-acting octreotide at 60 mg (114 patients) or ¹⁷⁷Lu-Dotatate plus long-acting octreotide at 30 mg (117 patients). Baseline characteristics were generally well balanced between the groups.

A prior analysis of NETTER-1 showed significantly longer progression-free survival (P <.001) and OS (P =.004) in the ¹⁷⁷Lu-Dotatate arm.2

The final analysis was performed 5 years after the last patient was randomized. The median follow-up was 76.3 months in the ¹⁷⁷Lu-Dotatate arm and 76.5 months in the control arm.

The median OS was 48.0 months in the ¹⁷⁷Lu-Dotatate arm and 36.3 months in the control arm (HR, 0.84; 95% CI, 0.60-1.17; P =.30).

The 1-year OS rate was 91.0% in the ¹⁷⁷Lu-Dotatate arm and 79.7% in the control arm. The 5-year OS rates were 37.1% and 35.4%, respectively.

Myelodysplastic syndrome (MDS) was reported in 2 patients who received ¹⁷⁷Lu-Dotatate, 1 of whom died 33 months after randomization. There were no new cases of MDS or acute myeloid leukemia during long-term follow-up.

Grade 3 or higher treatment-related serious adverse events (AEs) occurred in 7 patients in the ¹⁷⁷Lu-Dotatate arm. Nephrotoxicity of grade 3 or higher was observed in 6 patients in the ¹⁷⁷Lu-Dotatate arm and 4 in the control arm. One patient in the ¹⁷⁷Lu-Dotatate arm had grade 3 increased serum creatinine.

“Treatment with ¹⁷⁷Lu-Dotatate did not lead to a significant improvement in overall survival versus high-dose long-acting octreotide; however, an arguably clinically relevant difference in median overall survival of 11.7 months with ¹⁷⁷Lu-Dotatate was recorded, and was accompanied by a favorable long-term safety profile,” the researchers wrote.

“Along with the significantly reduced risk of disease progression or death and the associated quality-of-life benefits, these data further support the use of ¹⁷⁷Lu-Dotatate in this patient population with disease progression on somatostatin analogues,” the team concluded.

Disclosures: This research was supported by Advanced Accelerator Applications, a Novartis company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

  1. Strosberg JR, Caplin ME, Kunz PL, et al. 177 Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): Final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. Published online November 15, 2021. doi:10.1016/S1470-2045(21)00572-6
  2. Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. doi:10.1056/NEJMoa1607427

This article originally appeared on Cancer Therapy Advisor