P2.03b-083 Soluble Angiogenic Factors as Predictive Biomarkers of Response to Docetaxel plus Nintedanib as Second Line Therapy in NSCLC: Topic: Biomarkers

Abstract

Angiogenesis is fundamental for progression in non-small cell lung cancer (NSCLC). Nintedanib is a potent, triple angiokinase inhibitor of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). We evaluated the association between plasma levels of VEGF, FGF, and PDGF, both baseline and after treatment with Nintedanib plus Docetaxel, as well as disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), among patients with NSCLC. Thirty-eight patients were enrolled from July 2014 through October 2015. Stage IIIB/IV NSCLC patients who had progression after first-line chemotherapy with adenocarcinoma histology were included. Patients received Docetaxel 75mg/m2 on day 1 plus 200mg of Nintedanib orally twice daily on days 2-21 every three weeks until unacceptable adverse events or disease progression. Peripheral blood samples were taken at baseline and after completion of the second cycle of Docetaxel plus Nintedanib therapy to measure angiogenic factors. Mean age at diagnosis was 58.7 years. Eighty-two percent of the patients had metastatic disease, and a good (<2) ECOG performance status (97.4%). Acinar (21.1%) and papillary (15.8%) sub-histological types were the most common adenocarcinoma predominant patterns. Overall response rate and DCR were of 7.9% and 47.3%, respectively. Baseline values of FGF, VEGF and PDGF were 27.6 pg/ml; 122.7 pg/ml and 8,655 pg/ml. Patients with DCR were more likely to have lower median serological values of FGF at follow-up (33.1 vs. 88.1 pg/ml; p=0.0017). Median PFS was 3.7 months. Both in the univariate and multivariate analyses, a higher percentage change reduction in PDGF after treatment was associated with a longer PFS (6.37 vs. 3.58 months, p=0.059; Hazard ratio (HR): 3.15, p=0.024). OS of patients was 8.8 months. Both in the univariate and multivariate analysis a higher percentage change in FGF was associated with a longer OS (13.8 vs. 7.16 months, p=0.006; HR: 3.63, p=0.033]. A higher reduction of plasma levels of FGF and PDGF was associated with better clinical outcomes.