6533b7d1fe1ef96bd125d633

RESEARCH PRODUCT

The Vegf Pathway in Patients with Pancreatic Neuroendocrine Tumors: Efficacy of Everolimus by Baseline Marker Level, and Prognostic and Predictive Effect Analyses from Radiant-3

subject

description

ABSTRACT Background RADIANT-3 was a phase III study investigating the effect of the mammalian target of rapamycin inhibitor everolimus on progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET; Yao et al, NEJM, 2011). Everolimus significantly improved PFS compared with placebo (11 vs 4.6 months, P  Methods Baseline plasma levels of VEGF-A, PlGF, sVEGFR1, and sVEGFR2 were determined by ELISA using multiplexed MSD platform. The optimal cutoffs for these markers were explored using the “survival tree analysis” method. Interaction of treatment and baseline marker status ( Results PFS was significantly improved to a similar extent in patients receiving everolimus compared with patients who received placebo, regardless of baseline levels of markers (P  Conclusions These exploratory analyses demonstrated consistent everolimus efficacy in all patients with advanced pNET irrespective of their baseline VEGF pathway biomarker levels. However, levels of VEGF-A, PlGP, and sVEGFR1 are potential prognostic factors for pNET. Marker Cutoff (pg/mL) Median PFS Prognostic effect HR [95% CI]; P value Treatment effect P value VEGF-A 246.1 8.3 vs 5.5 1.50 [1.17-1.92]; PlGF 32.06 8.0 vs 4.2 1.52 [1.14-2.02]; .004 SVEGFR1 226.2 8.3 vs 5.5 1.62 [1.27-2.07]; SVEGFR2 24503.1 10.8 vs 5.7 1.30 [0.96-1.76]; .090 Disclosure J.C. Yao: Consultant/advisory role for Novartis, Ipsen, Pfizer, Endo; Honoraria from Novartis; Research funding from Novartis, Genentech. M. Shah: Honoraria for presentations and participation in Advisory Board Meetings: Novartis, Ipsen, Pfizer Research grant: Novartis. A. Panneerselvam: Novartis employee. S. Stergiopoulos: Novartis employee. D. Chen: Novartis employee. M. Pavel: Honoraria for presentations and participation in Advisory Board Meetings: Novartis, Ipsen, Pfizer Research grant: Novartis. All other authors have declared no conflicts of interest.