Epidermal growth factor receptor tyrosine kinase inhibitors in previously treated advanced non-small-cell lung cancer with wild-type EGFR

ABSTRACT

Introduction: While epidermal growth factor receptor (EGFR) – tyrosine kinase inhibitors (TKIs) lead to longer progression-free survival (PFS) when compared with conventional chemotherapy in non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR-TKI remains unclear in EGFR-wild-type (WT) NSCLC.

Areas covered: This article reviews selected data from randomized trials regarding the use of TKIs in EGFR-WT NSCLC. Nine randomized phase III trials have compared EGFR-TKI with chemotherapy in NSCLC patients in a second or later line setting. Two of these trials, TAILOR and DELTA, which were designed to investigate treatment benefits according to EGFR genotype, demonstrated that docetaxel chemotherapy displayed significantly better in progression-free survival (PFS) when compared with the EGFR-TKI erlotinib. Biomarkers to predict clinical benefits of the drug against EGFR WT tumor, and the efficacy of combination regimens using erlotinib or single-use afatinib against tumors are also covered in this article.

Expert opinion: Considering the modest benefits of erlotinib for EGFR-WT tumors, future studies are warranted, including the exploration of useful biomarkers and new treatment strategies for EGFT-TKI use, as well as the development of more sensitive EGFR mutation tests.

KEYWORDS:

• Chemotherapy
• EGFR tyrosine kinase inhibitor
• EGFR wild-type
• non-small cell lung cancer
• review

Article highlights

• The role of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-wild-type (WT) non-small-cell lung cancer (NSCLC) remain unclear. Based on previous clinical studies, erlotinib is significantly better than best supportive care in survival and less efficacious than docetaxel against this type of tumor. As an EGFR mutation test is not always definitive in some portion of NSCLC patients, the opportunity for patients to receive EGFR-TKIs should be maintained in clinical settings.

• Exploring biomarkers is critical, and the VeriStrat test is promising for guiding treatment decisions in previously treated patients with EGFR-WT NSCLC.

• Combination therapy with EGFR-TKIs is also promising, but the use of erlotinib alone as a reference arm in randomized trials for EGFR-WT tumors is no more effective.

• Afatinib was better than erlotinib in efficacy as a second-line treatment for patients with advanced squamous cell carcinoma. For the positioning of the drug, a comparison of efficacy between afatinib and docetaxel is necessary in EGFR-WT NSCLC.

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Declaration of interest

T Kawaguchi has received funding for research from Chugai Pharmaceutical. A Kubo has received funding for research from Chugai Pharmaceutical. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

ORCID

Shigeki Mitsuoka http://orcid.org/0000-0003-2428-5218

Tomohiro Suzumura http://orcid.org/0000-0002-3785-5155