In a European phase II/III trial (AXINET) reported in the Journal of Clinical Oncology, Garcia-Carbonero et al found that the addition of axitinib to long-acting octreotide appeared to show activity in patients with advanced extrapancreatic neuroendocrine tumors (epNETs).
Study Details
The double-blind trial included 256 patients with unresectable/metastatic G1-2 epNETs who had received up to two previous treatment lines from sites in Spain, Italy, and Germany. They were randomly assigned between October 2011 and May 2019 to receive axitinib at 5 mg (n = 126) or placebo (n = 130) twice daily plus intramuscular octreotide long-acting release at 30 mg every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival; progression-free survival was also assessed by blinded independent central review (BICR).
Key Findings
Investigator-assessed median progression-free survival was 17.2 months (95% confidence interval [CI] = 13.6–24.7 months) in the axitinib group vs 13.1 months (95% CI = 10.9–18.6 months) in the control group (hazard ratio [HR] = 0.86, 95% CI = 0.65–1.15, P = .324).
Median progression-free survival on BICR was 16.6 months (95% CI = 13.5–24.2 months) in the axitinib group vs 9.9 months (95% CI = 8.2–13.9 months) in the control group (HR = 0.71, 95% CI = 0.54–0.94, P = .017).
Objective response rates were significantly higher in the axitinib group vs the control group on both investigator assessment (17.5% vs 4.6%, P = .001) and BICR (12.8% vs 3.2%, P = .005).
The most common grade ≥ 3 treatment-related adverse events in the axitinib group were hypertension (30.0%), diarrhea (17%), asthenia (12%), and palmar-plantar erythrodysesthesia (6%); in the control group, they were hypertension (12%) and asthenia (5%). Treatment was discontinued due to treatment-related adverse events in 18% vs 3% of patients. Death potentially related to treatment occurred in one patient in the axitinib group (due to cardiac failure) and two patients in the control group (due to myocardial infarction and hepatorenal syndrome).
The investigators concluded: “Axitinib significantly increased [progression-free survival] per BICR assessment and [objective response rate] both per investigator and BICR assessment compared with placebo, although the primary study endpoint was not met. Toxicity profile was manageable with no new safety concerns.”
Rocio Garcia-Carbonero, MD, PhD, of Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE) and Pfizer. For full disclosures of the study authors, visit ascopubs.org.
