Multinational phase 2-3 trial of axitinib and long-acting octreotide in advanced extrapancreatic neuroendocrine tumors

Angiogenesis plays an essential role in neuroendocrine tumors (NETs). The phase 2-3 AXINET trial, at 27 centers in Spain, Italy, and Germany, evaluated axitinib in unresectable/metastatic extrapancreatic (ep)NETs in adult patients who had received up to two previous treatment lines. Patients were randomized to oral axitinib 5 mg (n=126) or placebo (n=130) twice daily, in combination with intramuscular long-acting octreotide 30 mg once every 28 days until disease progression or unacceptable toxicity. Randomization was stratified by primary tumor site, Ki-67 index, and time from diagnosis. The primary endpoint was investigator-assessed progression-free survival (PFS). The median investigator-assessed PFS was 17.2 months in the axitinib group and 13.1 months in the placebo group (HR 0.86; 95% CI 0.65-1.15), whereas the median PFS according to blinded independent central review (BICR) was 16.6 months versus 9.9 months (0.71; 0.54-0.94). The objective response rate was significantly greater for axitinib per investigator assessment (17.5% versus 4.6%; p=0.001) and per BICR (12.8% versus 3.2%; p=0.005). Most common grade ≥ 3 toxicities were hypertension (24.0% versus 9.2%) and diarrhea (13.6% versus 1.5%). The author conclude that axitinib significantly increased PFS per BICR assessment and ORR both per investigator and BICR assessment, although the primary study endpoint was not met.