J Thorac Oncol. 2019 Aug 06. pii: S1556-0864(19)30650-1. [Epub ahead of print]
Sai Yendamuri,
Joseph Barbi,
Sarabjot Pabla,
Cara Petrucci,
Achamaporn Punnanitinont,
Mary Nesline,
Sean T Glenn,
Paul Depietro,
Antonios Papanicalou-Sengos,
Carl Morrison,
Grace K Dy,
Peter L Elkin.
INTRODUCTION: Metformin, a common medication used in the treatment of Diabetes Mellitus is known to have anti-cancer effects. We hypothesized that the salutary effect of metformin on the survival of patients with stage I NSCLC is influenced by body mass index (BMI).
METHODS: Patients undergoing lobectomy for stage I NSCLC without neoadjuvant therapy were included. Univariate and multivariate survival analyses to examine the association between metformin use and overall, disease specific and recurrence free survival (OS, DSS and RFS respectively) were performed, stratified by BMI (>25 and <25). Expression of immune checkpoints in patients on metformin and not was performed in a separate cohort of 205 patients with advanced disease.
RESULTS: 434 stage I patients (including 74 metformin users) were deemed eligible for analysis. Univariate and multivariate analysis revealed an association between metformin use and OS (HR=0.52; P=0.04) as well as DSS (HR=0.21; P=0.04) but not RFS (HR=0.67; P=0.33) in high-BMI patients only. In a separate cohort of 205 tumors of all stages (including 35 metformin users), downregulation of immune checkpoint gene expression (PDCD1, CTLA4, BTLA, CD27, LAG3 and ICOS) in metformin users was seen only in high-BMI patients, with upregulation of these genes seen in low-BMI patients with metformin use.
CONCLUSIONS: Metformin use may be associated with better OS and DSS only in high-BMI patients. This hypothesis is supported by gene expression data of immune checkpoint genes in metformin users using a separate cohort of advanced stage tumors. Further studies examining the interaction of BMI with metformin in NSCLC are worthwhile.
Keywords: Diabetes; Lung cancer; Metformin; survival