Dr Reidy-Lagunes on the Evolving NET Treatment Paradigm

“[The year 2024] has been exciting in that we had 2 important studies that were reported that help us add to the therapies we have to offer to our patients with advanced NETs.”

Diane Reidy-Lagunes, MD, vice chair, Oncology Operations, Regional Care Network, Memorial Sloan Kettering Cancer Center, discusses key trials that have expanded the treatment paradigm for patients with neuroendocrine tumors (NETs).

The 2024 release of data from 2 pivotal phase 3 clinical trials, CABINET (NCT03375320) and NETTER-2 (NCT03972488), marked significant advancements in the management of advanced NETs, Reidy-Lagunes begins. These studies provided evidence supporting valuable additions to the treatment paradigm for this heterogeneous patient population, which includes patients with both indolent and aggressive forms of disease, she says.

The CABINET trial evaluated cabozantinib (Cabometyx), an oral TKI, in heavily pretreated patients with pancreatic and extrapancreatic NETs. Patients were randomly assigned in a 2:1 fashion to receive cabozantinib or placebo. Improved progression-free survival (PFS) outcomes were observed with cabozantinib in both the pancreatic and extrapancreatic patient cohorts, highlighting the efficacy of this agent following prior treatment with somatostatin analogs, everolimus, and other prior therapies, Reidy-Lagunes notes. In the extrapancreatic NET cohort, the median PFS was 8.4 months (95% CI, 7.6-12.7) with cabozantinib (n = 134) vs 3.9 months (95% CI, 3.0-5.7) with placebo (n = 69; HR, 0.38; 95% CI, 0.25-0.59; P < .001). In the pancreatic NET cohort, the median PFS was 13.8 months (95% CI, 9.2-18.5) with cabozantinib (n = 64) vs 4.4 months (95% CI, 3.0-5.9) with placebo (n = 31; HR, 0.23; 95% CI, 0.12-0.42; P < .001). This trial established cabozantinib as a promising therapy for patients with limited treatment options, she emphasizes.

The NETTER-2 trial investigated lutetium Lu 177 dotatate (Lutathera) in combination with octreotide in patients with intermediate- to high-grade gastroenteropancreatic NETs with a Ki-67 proliferation of up to 55%. The study compared this combination with high-dose octreotide monotherapy. Results revealed a median PFS of 22.8 months (95% CI, 19.4-not estimated) in the lutetium Lu 177 dotatate arm (n = 226), along with an overall response rate of 43.0% (95% CI, 35.0%-51.3%).

Both CABINET and NETTER-2 provide the basis for the growing treatment arsenal for advanced NETs, Reidy-Lagunes concludes.

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