A New Therapy Option for Treatment-Refractory Advanced Neuroendocrine Tumors

When neuroendocrine tumors progress despite treatment (i.e., somatostatin analogue therapy, sunitinib, everolimus, chemotherapy, and Lu-177 dotatate), patients have limited options. Investigators now report results of the randomized, phase-3 CABINET trial comparing the multitargeted tyrosine kinase inhibitor cabozantinib (60 mg/day) with placebo in 298 patients with treatment-refractory pancreatic or extrapancreatic neuroendocrine cancers (pancreatic primaries, 32%; extrapancreatic primaries, 68%). Most tumors were grade 2 (64%), followed by grade 1 (24%) and grade 3 (8%). Nearly all patients had prior somatostatin analogue therapy (95%), and most had previous treatment with Lu-177 dotatate (59%) and everolimus (72%).

The primary endpoint of median progression-free survival was significantly superior with cabozantinib compared with placebo in both the pancreatic cohort (4.4 vs. 13.8 vs. 4.4 months; hazard ratio, 0.23) and the extrapancreatic cohort (3.9 vs. 8.4 months; HR, 0.38).

Crossover from placebo to cabozantinib at progression occurred in 33% and 41% of the pancreatic and extrapancreatic cohorts, respectively. Overall survival (OS) results were immature at publication, although median OS was similar with cabozantinib and placebo in the pancreatic cohort (40.0 and 31.1 months; HR, 0.95) and extrapancreatic cohort (21.9 and 19.7 months; HR, 0.86). Tumor response to placebo was 0% in both cohorts; response to cabozantinib was 19% in the pancreatic cohort and 5% in the extrapancreatic cohort. No new safety signals were observed.