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• 12441

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  P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12475

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    P3.06-035 - Study of the correlations between SNPs in angiogenic genes and treatment response/ outcome in patients with advanced NSCLC (non-squamous histology) treated in first line with carboplatin, paclitaxel and bevacizumab (CPB). The ANGIOMET study. (ID 2664)

    09:30 - 09:30  |  Author(s): D. Rodriguez Abreu
    • Abstract

    Background
    It has been demonstrated that the addition of bevacizumab to paclitaxel plus carboplatin (CPB) in the treatment of advanced NSCLC improves survival. Even though, there is a high variability in drug efficacy between patients, leading to different response rates. ANGIOMET is an exploratory study promoted by the SLCG in advanced NSCLC, non-squamous histologies (NS-NSCLC) treated in first line with a combination scheme based in CPB, designed to investigate the relationship between angiogenic mediators and the outcome and response to treatment. The primary end-point was progression-free survival (PFS), and the secondary end-points are the follows: OS, response-rates and toxicity profiles.

    Methods
    In this multicentric study, patients with stage IIIB/IV NS-NSCLC (ECOG status 0–2) were included and treated in first line with CPB. Peripheral blood samples were collected before treatment administration and DNA was purified from the leukocyte fraction. Ten SNPs of VEGF-pathway genes were genotyped in 186 samples by RT-PCR in duplicate. SNPs were related to PFS and OS (Kaplan-Meir method, log-rank test) and to response rate.

    Results
    10 SNPs were determined in 186 DNA samples. In this preliminary analysis there were data from 108 patients valid for PFS and OS analysis. Baseline characteristics of the patients were: median age, 63 years [37-80]; 74.5% male; 94.1% ECOG PS 0-1; 14% never-smokers, 100% caucasian; 89.7% adenocarcinomas, 2.8% large cell carcinomas; median number of CPB cycles was 4. There was no response assessment in 27 patients (25%), 30.6% PR, 31.5% SD and 13.0% PD. The SNP rs833061 (CC) in VEGFA correlated with lower response rates to CPB than the other genotypes (p=0.07). SNPs in KRAS and VEGFR2 were associated with PFS and/or OS in our cohort. The KRAS SNP rs10842513 (TT+CT) was associated with shorter PFS compared with the CC genotype (median: 5.39 vs 6.81 months; p=0.04, respectively). The VEGFR2 SNP rs2071559 (AA) was significantly associated with longer PFS and OS (Table 1). No significant differences in PFS or OS were observed according to other SNPs analyzed. Table 1: PFS and OS for VEGFR2 SNPrs2071559.

    		PFS
    	%	Median (months)	95%CI	p
    VEGFR2 (rs2071559)
    AA	25.6	9,408	5,084 - 13,732	0.01
    GG+AG	74.0	5,724	4,902 - 6,546
    		OS
    	%	Median (months)	95%CI	p
    VEGFR2 (rs2071559)
    AA	25.6	NR	----	0.001
    GG+AG	74.0	12,270	8,760 – 15.780

    Conclusion
    These preliminary data indicate that genetic variation in VEGFR2, SNP rs2071559 variant AA, is associated with prognosis in advanced NS-NSCLC patients treated with CPB and may have predictive implications as biomarkers in patients treated with chemotherapy with bevacizumab. On behalf of the Spanish Lung Cancer Group (SLCG)