In a phase II trial (Alliance A021202) reported in the Journal of Clinical Oncology, Bergsland et al found that pazopanib prolonged progression-free survival vs placebo in patients with advanced extrapancreatic neuroendocrine tumors (epNETs). However, as stated by the investigators, pazopanib will not be pursued in this setting because of risk-benefit concerns.
Study Details
In the U.S. multicenter double-blind trial, 171 patients with low- to intermediate-grade epNETs with radiologic progressive disease within 12 months of study entry were randomly assigned between September 2013 and October 2015 to receive pazopanib at 800 mg (n = 97) or placebo (n = 74) once daily. Previous somatostatin analog (SSA) treatment was required for patients with midgut tumors, and concurrent SSA treatment was allowed. The primary endpoint was progression-free survival on blinded independent central review. Crossover from placebo to pazopanib was permitted at disease progression.
A total of 75% of patients had midgut tumors, 93% had prior SSA treatment, and 49% had functional tumors.
Key Findings
Median follow-up was 61 months (95% confidence interval [CI] = 60–63 months).
Median progression-free survival was 11.8 months (95% CI = 9.8–14.6 months) in the pazopanib group vs 7.6 months (95% CI = 5.7–9.1 months) in the placebo group (hazard ratio [HR] = 0.54, 95% CI = 0.37–0.79, P < .001); the rate at 12 months was 47.0% vs 21.5%.
A total of 49 placebo patients crossed over to receive pazopanib. No difference in overall survival was observed for the pazopanib group vs the placebo group (HR = 1.11, 95% CI = 0.73–1.69, P = .32); the rates at 12 and 24 months were 79.3% vs 88.1% and 64.4% vs 66.3%.
Grade ≥ 3 adverse events occurred in 84% of the pazopanib group vs 47% of the placebo group (P < .001), including higher rates of hypertension (36% vs 8%, P < .001) and hepatic enzyme elevation (12% vs 1%, P = .013) with pazopanib. Grade 5 adverse events were reported in 8% vs 0% of patients (P = .017).
The investigators concluded: “Pazopanib compared with placebo significantly improves [progression-free survival] in patients with progressive epNET, confirming that the VEGF signaling pathway is a valid target for therapy in epNET. However, after integrating the associated risks relative to the benefits, further development of pazopanib in this clinical context is not planned.”
Emily K. Bergsland, MD, of the Department of Medicine, University of California San Francisco, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and Novartis. For full disclosures of all study authors, visit ascopubs.org.
