Targeted therapies for patients with advanced NSCLC harboring wild-type EGFR: what's new and what's enough.

Fei Zhou,Cai-Cun Zhou

doi:10.1186/s40880-015-0036-4

Abstract

Historically, non-small cell lung cancer (NSCLC) is divided into squamous and nonsquamous subtypes based on histologic features. With a growing number of oncogenic drivers being identified in squamous and nonsquamous NSCLC, this malignancy has been recently divided into several distinct subtypes according to the specific molecular alterations. This new paradigm has substantially highlighted the treatment of advanced NSCLC, shifting it from standard chemotherapy according to specific histologic subtypes to targeted therapy according to specific oncogenic drivers. The application of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in NSCLC patients harboring activating EGFR mutations has been a representative model of precise medicine in the treatment of NSCLC. As the role of EGFR-TKIs in routine management of patients with advanced NSCLC has been well established, this review provides an overview of alternative targeted therapy in the treatment of NSCLC, including EGFR-TKIs for patients with wild-type EGFR NSCLC, as well as other targeted agents either clinical available or in early- to late-stage development.

Highlights

Lung cancer remains the leading cause of cancer-related deaths worldwide, of which non-small cell lung cancer (NSCLC) is the most frequent type [1,2,3]
As the role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in routine management of advanced NSCLC patients harboring activating EGFR mutations have been well established, this review focuses on alternative targeted therapy in the treatment of NSCLC, including EGFR-TKIs for patients with wildtype EGFR NSCLC
The tremendous advances of EGFR-TKIs represent a success of precise medicine in the treatment of NSCLC

Summary

Introduction

Lung cancer remains the leading cause of cancer-related deaths worldwide, of which non-small cell lung cancer (NSCLC) is the most frequent type [1,2,3]. In TAILOR study [18], patients assigned to the chemotherapy arm (docetaxel) experienced a statistically significant improvement in PFS (2.9 versus 2.4 months; HR, 0.71; 95% CI, 0.53–0.92; P = 0.02) and OS (8.2 versus 5.4 months; HR, 0.73; 95% CI, 0.53–1.00; P = 0.05) compared with erlotinib in second-line therapy for patients with advanced wild-type EGFR NSCLC.

Results

Conclusion