An analysis of mature overall survival data from a phase III trial showed that Afinitor increased median overall survival by 6.34 months compared to placebo, for a total of over 3.5 years in patients with well-differentiated advanced and progressive pancreatic neuroendocrine tumors.
Overall survival was a secondary endpoint of the trial. The findings were presented at the European Society for Medical Oncology Congress in Madrid. Results from the primary analysis, which focused on progression-free survival, in which Afinitor (everolimus) more than doubled median PFS compared to placebo, were previously published in the New England Journal of Medicine.
Results from the trial, named RADIANT-3, showed a median OS of 44.02 months (95% CI: 35.61, 51.75) in patients treated with Afinitor plus best supportive care, and 37.68 months (95% CI: 29.14, 45.77) in the placebo arm.
The 6.34 month difference between the two arms was not statistically significant (HR 0.94; 95% CI: 0.73, 1.20; p=0.300). According to the drug’s sponsor, Novartis, a high crossover of patients from placebo to Afinitor (85 percent) likely contributed to the long median OS in the placebo arm of 37.68 months, and may have confounded the ability to detect a difference in the OS results.
“The median overall survival of 44 months for everolimus is unprecedented in controlled clinical trials for advanced progressive pancreatic neuroendocrine tumors,” said lead investigator James Yao, of MD Anderson Cancer Center. “The results affirm the importance of targeting key pathways involved in tumor growth, such as the mTOR pathway in advanced pNET.”
RADIANT-3 is a prospective, double-blind, parallel group study. The core phase of the trial examined the efficacy and safety of Afinitor plus BSC versus placebo plus BSC in 410 patients with advanced, low- or intermediate-grade pancreatic NET, also known as islet cell tumors.
Patients who met the study entry criteria were randomized 1:1 to receive either everolimus 10 mg once-daily (n=207) or daily placebo (n=203) orally, both in conjunction with BSC.
Patients on placebo whose disease progressed during the core phase were allowed to cross over to open-label Afinitor. In addition, when all patients were unblinded at the end of the core phase, those initially assigned to placebo were offered to switch to open-label Afinitor and those in the Afinitor arm could transition to open-label Afinitor.
During the open label phase patients continued with treatment until disease progression was documented by the investigator. At this point, patients discontinued the study drug and entered the follow-up period to be monitored monthly for survival information. All patients initially randomized to placebo were included in the placebo arm results, even if they crossed over to everolimus therapy after progression or unblinding. In total, 85% of patients in the placebo arm crossed over to everolimus during the course of the study.
The safety profile was consistent with that observed for Afinitor in advanced pancreatic NET and no unexpected or new safety concerns were identified at the time of the analysis.
Afinitor is approved in more than 85 countries including the U.S. and European Union for locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin. It is also approved in more than 100 countries for advanced renal cell carcinoma following progression on or after vascular endothelial growth factor targeted therapy.
Novartis plans to submit this data to regulatory authorities for inclusion in Afinitor’s prescribing information.
