ANGIOMET: Analysis of the correlations between angiogenic markers and outcome in patients (p) with advanced nonsquamous NSCLC (NS-NSCLC) treated with carboplatin, paclitaxel, and bevacizumab (CPB).

Abstract

e19014 Background: In NS-NSCLC CPB achieved median OS > 1 y and supported use of B. A broad range of predictive/prognostic markers explored for B use. In VEGF pathway ligands and receptors play an important role in tumor angiogenesis and therapeutic efficacy. Altered levels of angiogenic factors in tumor or serum/plasma have been associated with prognosis and may be related with outcome when B is used. Methods: Advanced NS-NSCLC p were treated 1st-line with CPB. Primary end-point: PFS; secondary end-points: OS, RR, toxicity. Ancillary study designed to investigate relationship between angiogenic mediators, response and outcomes . 200 p St IIIB/IV NS-NSCLC and ECOG 0–2 prospectively included and treated with CPB 6 cycles followed by B maintenance. Ethical approval and informed consent for collecting peripheral blood samples and associated clinical data. Samples collected before treatment (basal) and at response evaluation (post). DNA obtained from leukocyte fraction (n=168). SNPs of angiogenic genes genotyped by PCR. Plasma levels of VEGFA and VEGFR2 determined by ELISA. Response RECIST.1 and toxicity CTCAEv.1. Results: P characteristics: median age 61 years [37-80], 67.2% male, 97.8% stage IV, 15.8% never-smokers, 100% caucasian, 88.2% adenoca. Median number of delivered CPB cycles 5. ITT RR (143 p): CR 1 (0.7%), PR 70 (48.9%), SD 52 (36.4%), PD 18 (12.6%), NE 2 (1.4%) Median PFS 6.91 months [6.16-7.65]; OS 14.57 months [11.83- 17.31]. No significant correlations between best response and the analyzed SNPs or plasmatic levels of VEGF and VEGFR2. VEGFR1 SNP rs9582036 (CC) was associated with shorter PFS (p=0.01) and OS (p=0.01). VEGFA SNP rs3025039 (CC) correlated with reduced OS compared with other genotypes (CT+TT) (p=0.009). No significant differences in PFS or OS were observed according to other SNPs . Lower levels (<median) of circulating VEGF (basal) with significant longer PFS (p=0.04 ) and a trend for OS (p=0.10). Conclusions: Multicentric trial with median OS 14.5 m achieved with CPB 1st-line in advanced NS-NSCLC p. Some VEGFR1 and VEGFA SNPs reduce CPB efficacy. In p with lower basal VEGF levels outcomes are improved. Clinical trial information: NCT01814163.