37PD - SNPs in angiogenic factors as predictive markers for outcome in patients (p) with advanced non-squamous NSCLC (NS-NSCLC) treated with carboplatin, p...

Date 16 April 2015
Event ELCC 2015
Session Medical and radiation oncology
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Bartomeu Massuti Sureda
Citation Annals of Oncology (2015) 26 (suppl_1): 10-14. 10.1093/annonc/mdv045
Authors B. Massuti Sureda1, E. Jantus-Lewintre2, J.L. Gonzalez-Larriba3, D. Rodriguez Abreu4, O.J. Juan5, M. Domine6, M. Provencio Pulla7, J. de Castro8, C. Camps9, R. Rosell10
  • 1Medical Oncology, Hospital General Universitario de Alicante, 03010 - Alicante/ES
  • 2Molecular Oncology, Fundación Investigación Hospital General Universitario de Valencia, Valencia/ES
  • 3Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 4Medical Oncology Service, Hospital Universitario Insular de Gran Canaria, 35016 - Las Palmas/ES
  • 5Medical Oncology, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 6Oncology, University Hospital "Fundacion Jimenez Diaz", 28040 - Madrid/ES
  • 7Oncology, Hospital Universitario Puerta de Hierro Majadahond, 28222 - Majadahonda/ES
  • 8Medical Oncology, Hospital Universitario La Paz, Madrid/ES
  • 9Department Of Medicine, Universitat de València, 46010 - Valencia/ES
  • 10Medical Oncology Service, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 08916 - Badalona/ES

Abstract

Aim/Background

Addition of Bev to CP achieved median OS > 1 year in advanced NS-NSCLC p. A broad range of predictive/prognostic markers explored for Bev use. In VEGF pathway both ligands and receptors play an important role in tumor angiogenesis and therapeutic efficacy. SNPs could modify levels of angiogenic factors in tumor or serum/plasma associated with prognosis and may be related with outcomes when Bev is used.

Methods

Advanced St IIIB/IV NS-NSCLC p with ECOG 0-2 prospectively included and treated 1st-line with CP-Bev 6 cycles followed by Bev maintenance. Primary end-point: PFS; secondary end-points: OS, RR, toxicity. Ancillary study designed to investigate relationship between angiogenic mediators, response and outcomes. 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. SNPs of angiogenic genes genotyped by PCR. Plasma levels of VEGFA and VEGFR2 determined by ELISA. Response RECIST.1 and toxicity CTCAEv.1.

Results

202 p included: median age 61 years [37-80], 67.2% male, 97.8% stage IV, 15.8% never-smokers, 100% caucasian, 88.2% adenoca. 199 p per protocol population, median number of delivered CPB cycles 5. ITT RR (171 p): CR 1%, PR 49%, SD 36 %), PD 10.6%, NE 4%. Median PFS 6.91 months [6.16-7.65]; OS 14.57 months [11.83- 17.31]. 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). Lower levels (

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. Final analysis of efficacy and predictive biomarkers will be presented.

Clinical trial identification NCT01814163

Disclosure

B. Massuti Sureda, J.L. Gonzalez-Larriba and O.J. Juan: Advisory board for Roche.

E. Jantus-Lewintre, M. Provencio Pulla, C. Camps and R. Rosell: Research funds from Roche.

J. de Castro: Advisory Board and Research Funds from Roche.

All other authors have declared no conflicts of interest.