EP1.01-35 Concurrent Use of Low Dose Aspirin and Vitamin D in ALK, ROS and EGFR Mutant NSCLC: A Single Institution Retrospective Analysis

Abstract

Tyrosine kinase inhibitors (TKI) are the backbone therapy for EGFR, ALK and ROS positive (pos) non-small cell lung cancer (NSCLC). Pre-clinical data suggest that low vitamin D level facilitates the growth of mutant EGFR NSCLC through Vitamin D receptor (VDR). VDR is highly expressed in EGFR lung cancer cells, and its interaction with activated 1,25 vitamin D3 (1,25D3) promotes epithelial differentiation and apoptosis while inhibiting cellular proliferation and angiogenesis. Thus vitamin D3 supplementation may potentially add anti-cancer activity to conventional therapy in this population. On the other hand, murine models have shown that prolonged use of aspirin reduces the incidence of distant metastases. It is postulated that biosynthesis of prostaglandins generate a permissive intravascular metastatic niche, through platelet aggregation and endothelial activation. Recent meta-analysis published by Feng et al. analyzed seventeen studies and reported statistically significant reduction in risk of lung cancer by 8% when circulating 25-VD is at 10 nmol/L, this benefit was seen in both Caucasian and Asian population. To our knowledge, there have been no studies looking at influence of concurrent vitamin D or aspirin intake on outcomes in ALK, ROS and EGFR pos NSCLC treated with tyrosine kinase inhibitors. We performed a retrospective single institution analysis to study this association. Patients (pts) with ALK, ROS EGFR pos NSCLC treated with first line TKI from January 2014 to June 2017 were included. Information on concurrent use and doses of aspirin and vitamin D supplements were studied. Patients were dichotomized based on use of these individual supportive medications. Two sample t-test was used to compare mean PFS and chi-square test to compare proportions of disease control rate (DCR) at 3 months between groups. 74 patients were included. PFS in Vitamin D supplementation (n=41, 55%) group was 11 months compared to 10.2 m in those not on Vitamin D (p = 0.21, CI 1.9). For those on aspirin (n=23, 35%), mean PFS was 16m vs 12.5 m (p = 0.7213; 95% CI -5.5812 to 3.8812). DCR for aspirin use was 50% vs 65% (p = 0.1796) and for vitamin D 48.6% vs 43.7% (p= 0.6989). Our study did not show any differences in PFS or DCR in EGFR, ROS and ALK positive NSCLC patients who were concurrently taking vitamin D or aspirin compared with those who were not. Our study was small and was not powered to pick up any significant differences. Given the strong pre-clinical background, further prospective studies would be interesting to evaluate the synergistic benefit of vitamin D and aspirin with concurrent TKI use.