Overall Survival With Everolimus in Advanced Pancreatic Neuroendocrine Tumors in the RADIANT-3 Trial
As reported by Yao et al in the Journal of Clinical Oncology, the final overall survival analysis from the phase III RADIANT-3 trial showed a median survival of 44.0 months among patients with advanced pancreatic neuroendocrine tumors initially randomized to receive everolimus (Afinitor, Zortress) treatment.
Study Details
In the trial, 410 patients with advanced progressive low- or intermediate-grade pancreatic neuroendocrine tumor were randomized to receive everolimus at 10 mg/d (n = 207) or placebo (n = 203); treatment continued until disease progression, development of unacceptable toxicity, withdrawal of consent, or primary analysis. Crossover to open-label everolimus was permitted after disease progression in the placebo group. The trial showed a significant improvement in progression-free survival, the primary endpoint, for everolimus vs placebo. After the primary analysis, all patients continuing in the study were unblinded and rolled over into an open-label extension phase; treatment with open-label everolimus continued until radiologically assessed disease progression.
Overall Survival
Among the 410 patients, 225 received open-label everolimus, including 85% of patients (n = 172) initially randomized to receive placebo. Median overall survival was 44.0 months among patients initially randomized to receive everolimus and 37.7 months among those initially randomized to receive placebo (hazard ratio = 0.94, P = .30).
Assessment of the impact of biomarkers on overall survival showed that elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble VEGFR1 (vascular endothelial growth factor receptor 1) levels were poor prognostic factors.
The investigators concluded: “Everolimus was associated with a median [overall survival] of 44 months in patients with advanced, progressive pancreatic [neuroendocrine tumor], the longest [overall survival] reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the [overall survival] results.”
The study was supported by Novartis.
James C. Yao, MD, of the University of Texas MD Anderson Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
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