A phase I/II study using cabozantinib and lanreotide as treatments for advanced GEP-NETs for which molecular targeted therapy or chemotherapy have failed (SCALET): TCOG T2221 study.
Abstract
Background
Somatostatin analogs (SSAs) and targeted therapies have shown efficacy for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in the past decades. To explore the therapeutic efficacy of SSA and targeted therapy combination, we conducted a phase I/II study to evaluate the toxicity and efficacy of cabozantinib and lanreotide in patients with advanced grade 1/2 or 3 progressive GEP-NETs for which molecular targeted therapies or chemotherapy have failed (SCALET trial). PATIENTS AND
Methods
Lanreotide (120 mg) was given on day 1 every 4 weeks. A 3 + 3 design was used in phase I to determine the maximum tolerated dose of cabozantinib (40 or 60 mg daily). The primary endpoint in phase II was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival, and toxicity of this regimen.
Results
A total of 42 patients were enrolled and treated. Among the 10 patients in phase I, no dose-limiting toxicity was observed. The recommended dose for cabozantinib was 60 mg daily for the 32 patients in phase II. Among the 31 patients evaluated per protocol, the median PFS (mPFS) was 25.2 months [95% confidence interval (CI) 6.7-43.7]. The mPFS in patients with pancreatic NET and extra-pancreatic NET were 27.5 months (95% CI 22.4-32.6) and 12.0 months (95% CI 7.2-16.8), respectively. The ORR was 35.5%. The median overall survival was not reached. These toxicities were comparable to those of cabozantinib and lanreotide reported in other trials.
Conclusion
This phase I/II study highlights the efficacy of cabozantinib and lanreotide for advanced GEP-NETs (NCT05048901).