Presence of Chronic Obstructive Pulmonary Disease (COPD) Impair Survival in Lung Cancer Patients Receiving Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI): A Nationwide, Population-Based Cohort Study.

Chia-Che Wu,Wei-Chieh Lee,Meng-Che Hsieh,Jia-Sin Liu,Yen-Yang Chen,Kun-Ming Rau,Harvey Yu-Li Su

doi:10.3390/jcm8071024

Abstract

The emergence of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) caused a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). Although several clinicopathologic factors to predict the response to and survival on EGFR-TKI were recognized, its efficacy has not been confirmed for patients with underlying pulmonary disease, such as chronic obstructive pulmonary disease (COPD). We conducted the study to evaluate the impact of COPD on survival for NSCLC patients that underwent EGFR-TKI treatment. The nationwide study obtained clinicopathologic data from the National Health Insurance Research Database in Taiwan between 1995 and 2013. Patients receiving EGRR-TKI were divided into COPD and non-COPD groups, and adjusted for age, sex, comorbidities, premium level and cancer treatments. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan–Meier analysis. In total, 21,026 NSCLC patients were enrolled, of which 47.6% had COPD. After propensity score (PS) matching, all covariates were adjusted and balanced except for age (p < 0.001). In the survival analysis, the median OS (2.04 vs. 2.28 years, p < 0.001) and PFS (0.62 vs. 0.69 years, p < 0.001) of lung cancer with COPD were significantly worse than those without COPD. Lung cancer patients on EGFR-TKI treatment had a worse survival outcome if patients had pre-existing COPD.

Highlights

Lung cancer is a global common malignancy, and accounts for the leading cause of cancer-related death in the USA, Asia and Taiwan [1,2]
We identified a total of 21,026 lung cancer patients treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) during the study period
Nationwide, population-based cohort study, we demonstrated that chronic obstructive pulmonary disease (COPD) is a crucial prognostic factor for lung cancer patients treated with EGFR-TKI

Summary

Introduction

Lung cancer is a global common malignancy, and accounts for the leading cause of cancer-related death in the USA, Asia and Taiwan [1,2]. Much progress in treatment of metastatic non-small cell lung cancer (NSCLC) has been made in recent decades, the 5-year survival of NSCLC in Taiwan remains poor (all stages, 16.3%). For NSCLC harboring EGFR driver mutation, the current standard of treatment in the first-line setting is EGFR tyrosine kinase inhibitor (TKI), either first-generation (gefitinib or erlotinib) or second-generation TKI (afatinib) [3,4,5,6]. A recent study, analyzing six randomized clinical trials, compared EGFR-TKI with conventional chemotherapy in the first-line setting and showed a significant increment in progressive-free survival (PFS) from 5.6 months with chemotherapy to 11.0 months with EGFR-TKI [7]. The presence of activating EGFR mutation (del or L858R) precisely predicts good response to EGFR-TKI, there are, several clinical factors showing various responses to EGFR-TKI, and the underlying mechanism still remains unknown [8]

Methods

Results

Conclusion