Comparison of outcomes of tyrosine kinase inhibitor in first- or second-line therapy for advanced non-small-cell lung cancer patients with sensitive EGFR mutations.

Jianlin Xu,Guozheng Ding,Xueyan Zhang,Bo Jin,Haitang Yang,Yanwei Zhang,Yuqing Lou,Huimin Wang,Baohui Han

doi:10.18632/oncotarget.12035

Jianlin Xu, Guozheng Ding + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.12035

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Journal: Oncotarget	Publication Date: Sep 15, 2016
Citations: 13	License type: cc-by

Affiliation: Shanghai Chest Hospital, Anqing City Hospital

Abstract

Direct comparisons between the use of first- and second-line EGFR tyrosine kinase inhibitor (TKI) in patients with sensitive EGFR mutations are limited. A total of 264 advanced non-small-cell lung cancer (NSCLC) patients with sensitive mutations received EGFR TKI therapy as the first-line therapy, and a total of 187 patients received TKI as the second-line therapy at Shanghai Chest Hospital. First-line EGFR TKI therapy [12.9 months, 95% confidence interval (CI), 10.7–15.2] provided longer progression-free survival (PFS) than did second-line EGFR TKI therapy (9.0 months, 95% CI, 7.7–10.2) [hazard ratio (HR): 0.78, P = 0.034]. The objective response rate (ORR) of first-, and second-line TKI therapy were 67.8% (159/233) and 55.6% (94/169), respectively (P = 0.001). The overall survival (OS) for patients (n = 141) receiving first-line TKI followed by second-line chemotherapy were longer than those for patients (n = 187) receiving first-line chemotherapy followed by second-line TKI (HR: 0.69, P = 0.02).Compared with second-line TKI, first-line therapy achieved a significant and longer PFS, and higher ORR in the sensitive EGFR mutated NSCLC patients. The therapeutic strategy of using TKI followed by chemotherapy achieved longer OS than that using chemotherapy followed by TKI.

Highlights

Worldwide, lung cancer is the most frequently diagnosed cancer
The results demonstrated that first-line tyrosine kinase inhibitor (TKI) therapy provided superior response rates (RR) and progressionfree survival (PFS) than secondline TKI therapy, and patients receiving first-line TKI followed by second-line chemotherapy experienced a longer overall survival (OS) than those who received first-line chemotherapy followed by second-line TKI therapy
Current guidelines suggest first-line TKI therapy for this population, based on the results of superior PFS and RR of first-line TKI, compared to chemotherapy [16]. Most of these studies failed to demonstrate improvement in OS. This raises the question of whether TKI is more effective in EGFR mutated non-small-cell lung cancer (NSCLC) as a first-line therapy or is effective when administered as a second-line therapy [15]

Summary

Introduction

Lung cancer is the most frequently diagnosed cancer. Non-small-cell lung cancer (NSCLC) constitutes approximately 85%–90% of all lung cancers [1, 2]. Platinum-based chemotherapy provides a survival benefit for patients with advanced lung cancer; most patients cannot survive more than 1 year [3]. Several randomized studies demonstrated that, for EGFR mutated NSCLC, first-line TKI therapy could provide higher tumor response rates (RR) and longer progression-free survival (PFS) than chemotherapy. Most of these studies failed to demonstrate improvement in overall survival (OS) [7,8,9,10,11,12]. Patients with EGFR mutations may benefit from second- or third-line EGFR TKI therapy. This raises the question of whether TKI is more effective in EGFR mutated NSCLC patients as a first-line therapy or is effective when administered as a second-line therapy [15]

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Results

Conclusion