The role of low dose aspirin, vitamin D, or metformin in EGFR, ALK, and ROS positive non-small cell lung cancer: A single institution retrospective analysis.

Abstract

e20656 Background: Tyrosine kinase inhibitor (TKI) is the backbone therapy for EGFR, ALK and ROS positive (pos) non-small cell lung cancer (NSCLC). Metformin has shown to sensitize EGFR resistant lung cancer cells in vitro through IL-6/STAT pathways. COX-2 overexpression triggers activation of a transcription factor that binds to EGFR that activates MAPK signaling pathway. Vitamin D receptor (VDR) has shown to directly inhibit EGFR transcriptional activity. Some studies have shown that adding metformin, aspirin and vitamin D (MAD) to chemotherapy may improve progression free survival (PFS) and overall survival (OS) in lung cancer. However, data supporting use of MAD is unknown in EGFR, ALK and ROS pos NSCLC. Methods: Patients (pts) with EGFR, ALK, ROS pos NSCLC treated with first line TKI from January 2014 to June 2017 were included. Information on concurrent use of MAD was obtained. 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. Results: 74 patients were included. Vitamin D supplementation (n = 38, 51.3%) prolonged PFS by 16 m vs 11 m (p = 0.04; 95%CI 0.23 to 9.34). For those on aspirin (n = 23, 35%), mean PFS was 16m vs 12.5 m (p = 0.72; 95% CI -5.58to 3.88). Mean PFS for pts on metformin (n = 8, 10%) was 14 months (m) vs 13.5 m for those who were not (p = 0.93, 95% CI -7.27 to 7.87). DCR for metformin use was 26.5% vs 89% (p = 0.0001); for aspirin was 50% vs 65% (p = 0.17) and for vitamin D 48.6% vs 43.7% (p = 0.69). Conclusions: To our knowledge, no data has been published regarding use of MAD in NSCLC with driver mutations. In our study, concurrent use of vitamin D with TKI prolonged PFS in these pts. However, this effect was not seen with metformin or aspirin. Our study was limited by retrospective design, possible under-reporting of medication use by patients and small patient population. Further prospective studies using these medications is important to evaluate the synergistic benefit with the approved targeted therapy.