Axitinib + Octreotide Shows PFS Benefit in Extrapancreatic NETs per Central Review (HR 0.71)

The AXINET (GETNE 1107) trial was an international, randomized, double-blind, placebo-controlled, phase II/III study evaluating the efficacy and safety of axitinib in combination with long-acting octreotide for patients with advanced extrapancreatic neuroendocrine tumors (epNETs). The study enrolled patients aged 18 years and older with unresectable or metastatic G1-2 epNETs who had received up to two previous lines of treatment. From October 2011 to May 2019, 256 patients were randomly assigned (1:1) to receive either oral axitinib 5 mg twice daily or placebo, both in combination with intramuscular octreotide long-acting release 30 mg every 28 days, until disease progression or unacceptable toxicity. Randomization was stratified by primary tumor site, Ki-67 index (≤5% or >5%), and time from diagnosis (> or ≤12 months). The primary endpoint was investigator-assessed progression-free survival (PFS). Efficacy was also assessed by a blinded independent central review (BICR).

Investigator-assessed median PFS was 17.2 months (95% CI, 13.6 to 24.7) in the axitinib group versus 13.1 months (95% CI, 10.9 to 18.6) in the placebo group (hazard ratio [HR], 0.86; 95% CI, 0.65 to 1.15). The median PFS per BICR was 16.6 months (95% CI, 13.5 to 24.2) for axitinib versus 9.9 months (95% CI, 8.2 to 13.9) for placebo (HR, 0.71; 95% CI, 0.54 to 0.94; p = .017). The objective response rate (ORR) was significantly greater for axitinib per both investigator assessment (17.5% vs 4.6%; p = .001) and BICR (12.8% vs 3.2%; p < .005). The most common grade ≥3 toxicities in the axitinib group were hypertension (24.0% vs 9.2% with placebo) and diarrhea (13.6% vs 1.5% with placebo). The study concluded that axitinib significantly increased PFS per BICR assessment and ORR per both investigator and BICR assessment compared with placebo, although the primary study endpoint of investigator-assessed PFS was not met. The toxicity profile was manageable with no new safety concerns.