Low Body Mass Index Is An Independent Prognostic Factor In Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

Background: Sarcopenia and obesity have been suspected as factors associated with efficacy of treatment and prognosis in various malignancies. This study aimed to investigate the association of pretreatment sarcopenia and visceral obesity with efficacy and prognosis of first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for patients with non-small cell lung cancer (NSCLC) and positive EGFR mutation.Methods: We retrospectively collected 167 NSCLC patients with mutant EGFR who had started EGFR-TKI monotherapy between October 2007 and August 2018 at our hospital. We classified 167 patients into two groups, according to the definition of underweight based on the World Health Organization (WHO) body mass index (BMI) classification and the Japanese sex-specific cut-off values of the following computed tomography (CT) images-assessed markers of pretreatment sarcopenia or visceral obesity, such as psoas muscle index (PMI), intramuscular adipose tissue content (IMAC) and visceral-to-subcutaneous fat ratio (VSR) at lumbar vertebra L3 level. We compared overall survival (OS) and progression-free survival (PFS) of two groups by Kaplan-Meier curves and log-rank tests. Using multivariate Cox proportional hazard analyses adjusted by age, neutrophil-to-lymphocyte ratio, performance status, EGFR mutation types and EGFR-TKI lines, and extra-pulmonary metastases or three or more than 3 metastatic sites, we searched independent prognostic factors of OS and PFS of EGFR-TKI therapy.Results: The OS (median 26.0 vs. 32.3 months, P = 0.02) and PFS (9.1 vs. 14.8 months, P = 0.03) of patients with BMI < 18.5 were significantly shorter than those of patients with BMI >= 18.5. However, there was no significant difference in OS and PFS according to PMI, IMAC and VSR. The multivariate analyses detected only BMI < 18.5 as an unfavorable prognostic factor of shorter OS (hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.03 - 2.81, P = 0.04) and PFS (HR 1.72, 95% CI 1.11 - 2.67, P = 0.02).Conclusions: Pretreatment underweight was a significant prognostic factor of poor PFS and OS of EGFR-TKI therapy. However, neither pretreatment sarcopenia nor visceral obesity was associated with prognosis of EGFR-TKI. Underweight may be a surrogate for advanced disease burden.