Baseline VEGF as a potential predictive biomarker of vandetanib clinical benefit in patients with advanced NSCLC

Abstract

8009 Background: Vandetanib (V) is a once-daily oral agent that selectively inhibits VEGFR, EGFR and RET signaling. Three randomized Phase II studies of V in advanced NSCLC have demonstrated improved progression-free survival (PFS) with V: V300 mg vs gefitinib (6474IL0003) and V100 mg ± docetaxel (D) vs D (6474IL0006) in previously treated NSCLC; V300 mg ± paclitaxel (P) and carboplatin (C) vs PC (6474IL0007) in 1st-line NSCLC. However, in 6474IL0007, V300 mg monotherapy was inferior to PC in terms of PFS. An exploratory analysis of the potential relationship between baseline VEGF levels and PFS was investigated in patients (pts) from these 3 studies. Methods: Two baseline plasma samples were collected from 163/168 pts (6474IL0003) and 44/83 pts (6474IL0006). Two baseline serum samples were collected from 144/181 pts (6474IL0007). Mean baseline VEGF levels were determined for each pt by ELISA. High baseline VEGF values were above the immunoassay reference range for healthy subjects (>115 pg/mL in plasma, >707 pg/mL in serum) and low baseline VEGF values were within this reference range. Results: In 6474IL0003, pts with low baseline VEGF had a lower risk of disease progression when treated with V vs gefitinib (HR = 0.55, 95% confidence interval [0.35, 0.86]). Conversely, pts with high baseline VEGF had similar benefit from both agents (HR = 1.03 [0.60, 1.75]). In 6474IL006, pts with low baseline VEGF had a lower risk of disease progression when treated with V100 mg + D vs D (HR = 0.25 [0.09, 0.68]), whereas disease progression was similar in both treatment groups for pts with high baseline VEGF (HR = 0.95 [0.25, 3.61]). In 6474IL0007, pts with low baseline VEGF had a lower risk of disease progression when treated with V300 mg vs PC (HR = 0.72 [0.38, 1.38]) whereas those with a high baseline VEGF progressed more quickly when treated with V300 mg vs PC (HR = 1.62 [0.88, 2.98]). There was no evidence that pts with low or high baseline VEGF had differential benefits when treated with V300 mg + PC vs PC (HR = 0.77 [0.42, 1.40] {low}; HR = 0.66 [0.31, 1.43] {high}). Conclusions: These exploratory analyses suggest low baseline levels of circulating VEGF may be predictive of PFS advantage in pts with NSCLC receiving V300 mg monotherapy vs gefitinib or PC, or V100 mg in combination with D vs D alone. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology AstraZeneca Oncology AstraZeneca Oncology AstraZeneca Oncology