Comparison of Different Tyrosine Kinase Inhibitors for Treatment of Poor Performance Status Patients with EGFR-Mutated Lung Adenocarcinoma

Chiao-En Wu,Cheng-Ta Yang,Chih-Hsi Kuo,Ching-Fu Chang,John Chang,Ping-Chih Hsu,Chen-Yang Huang

doi:10.3390/cancers14030674

Abstract

Simple SummaryEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments in patients with EGFR-mutated lung adenocarcinoma. However, the clinical data regarding EGFR-TKI efficacy in patients with poor performance status (PS ≥ 2) are limited. We reviewed the clinical outcomes and safety of EFGR-TKI use in patients with poor PS and identified the independent and favorable prognostic factors for progression-free survival and overall survival. We found that patients treated with 40 mg afatinib had better survival results, although only a non-significant trend toward superiority was observed in the multivariable analysis. Dose adjustment was an independent prognostic factor for PFS and OS. This study provided evidence of the use of EGFR-TKIs for patients with poor PS.The aim of this retrospective study was to investigate the tolerability and survival outcomes of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment in patients with a performance status ≥ 2. The data for 517 patients treated with EGFR-TKIs between January 2011 and January 2018 at a regional hospital in northern Taiwan were analyzed. Clinical and pathological features were collected, and univariate as well as multivariable analyses were undertaken to identify potential prognostic factors. The overall objective response rate, median progression-free survival (PFS), and median overall survival (OS) were 56.3%, 11.4 months, and 15.3 months, respectively. The mutation status (exon 19 deletion), locally advanced disease, dose adjustment, and the lack of liver and pleural metastasis were independent and favorable prognostic factors for PFS. Age < 60 years, mutation status (exon 19 deletion), dose adjustment, and lack of lung, liver, and no pleural metastasis were independent and favorable prognostic factors for OS. GFR-TKIs demonstrated acceptable efficacy and safety in the current cohort. Dose adjustment was identified as an independent prognostic factor for both PFS and OS, regardless of which EGFR-TKIs were used. The current research provided novel evidence of the clinical prescription of frontline EGFR-TKIs for EGFR-mutated lung adenocarcinoma patients with a PS score ≥2.

Highlights

In a large retrospective cohort study in Taiwan, patients treated with afatinib were younger and were less likely to have an Eastern Cooperative Oncology Group (ECOG)-performance status (PS) = 2 compared with those treated with gefitinib or erlotinib, the implication being that a physician’s tyrosine kinase inhibitors (TKIs) preference can be based on differing population groups
A total of 517 epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma patients with ECOGPS ≥ 2 who were treated with either gefitinib, erlotinib, or afatinib as first-line systemic treatments were included
The results showed that patients treated with 40 mg afatinib were significantly younger than those who received gefitinib and erlotinib

Summary

Introduction

Drug development, and clinical trials have resulted in the recommendation that patients diagnosed with advanced non-small-cell lung cancer (NSCLC) who harbor activating mutations in the epidermal growth factor receptor (EGFR) gene be treated with tyrosine kinase inhibitors (TKIs) as the first-line treatment [1,2].The currently recommended EGFR-TKIs include first-generation, such as gefitinib and erlotinib [3,4,5,6], and second-generation, such as dacomitinib and afatinib, which act as pan-human EGFR (HER) family inhibitors that irreversibly bind to EGFR [7,8,9,10]. Drug development, and clinical trials have resulted in the recommendation that patients diagnosed with advanced non-small-cell lung cancer (NSCLC) who harbor activating mutations in the epidermal growth factor receptor (EGFR) gene be treated with tyrosine kinase inhibitors (TKIs) as the first-line treatment [1,2]. Osimertinib demonstrated excellent survival outcomes contrasted with standard treatments (erlotinib or gefitinib) when used as a frontline treatment [12,13], first- and second-generation TKIs remain widely used in daily practice because sequential TKI treatment may benefit patients who develop T790M mutation, and this strategy is cost-effective [14,15]. Whether the second-generation TKI afatinib is a feasible treatment plan for ECOG-PS ≥ 2 NSCLC patients as opposed to first-generation gefitinib and erlotinib, when efficacy and safety are factored, remains unknown. This study aimed to investigate the safety and efficacy of various EGFR-TKIs treatments in patients diagnosed with EGFR-mutated NSCLC and poor PS (PS ≥ 2)

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