Abstract A6: Association of clinical outcomes and the change in circulating soluble VEGF receptor 2 (VEGFR2) levels in advanced gastric cancer patients treated with telatinib (Tel), capecitabine (X), and cislatin (P).

Background: Serum VEGFA concentrations and association with metastasic disease/and or poor outcome has been well documented in gastric cancer (GC) patients (pts). However, VEGFA has not been a useful predictor for outcome of treatment with VEGF pathway inhibitors. The soluble form of the VEGF receptor 2 (sVEGFR2) neutralizes circulating VEGF and functions as a negative feedback mechanism to enable partial inhibition of angiogenesis. Reduction in circulating sVEGFR2 levels has been shown upon treatment with multiple small molecule VEGFR inhibitors. Tel is a potent, oral and selective inhibitor of VEGFR 1, 2 and 3 and PDGF receptors. We investigated if marked decrease in the concentration of sVEGFR2 from baseline in response to Tel treatment were associated with lower risk of progression and death compared to pts with smaller decreases or no decrease from baseline. Methods: TEL0805, a phase 2 study, administered Tel with X and P (TEL-XP) as first-line treatment for advanced GC pts. Tel was administered at 900 mg bid beginning day (d)-7 (lead-in for PK/PD analysis) continuously until progression, X was administered d1–14, and P d1 of each 21 day cycle. Serum samples for sVEGR2 analysis were collected on d-7 (baseline) and d1 prior to treatment of the first and every other cycle. Pts whose maximum percentage decrease from baseline was >33% were considered to have “larger” decreases in sVEGFR2. Pts whose maximum percentage decrease from baseline was Results: Twenty-eight pts (25 metastatic, 3 stage III) had sVEGFR2 levels available for analysis. The median baseline sVEGR2 levels were 6,780 pg/mL (range 3,750 to 9,100). Treatment with Tel alone demonstrated onset of reduction of sVEGFR2 by d 7 of the first cycle. Reductions were achieved regardless of tumor histology or disease location. The median of the distribution corresponds to a maximum decrease from baseline of 25%. The duration of OS and PFS were both significantly longer for pts with ≥33% in sVEGFR2 relative to pts with Conclusions: In GC pts treated with the TEL-XP regimen, larger percentage decreases in the concentration of sVEGFR2 from baseline were associated with lower risk of progression and death compared to pts with smaller decreases or no decrease from baseline. Further study of sVEGR2 levels as a predictor of response to TEL-XP will be explored in a randomized setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A6.