Afatinib and Erlotinib in the treatment of squamous-cell lung cancer

ABSTRACT

Introduction

Squamous-cell carcinoma (SCC) of the lung represents around 20% of non-small cell lung cancers. Although activating mutations of EGFR are rare in this subtype, its overexpression occurs in more than half the cases. Consequently, many epidermal growth factor receptor (EGFR)-targeted agents have been investigated in patients with SCC.

Areas covered

This review summarizes the potential roles of erlotinib and afatinib in SCC of the lung. The authors explore the rationale of targeting EGFR in SCC and the pharmacological properties of erlotinib and afatinib. Subsequently, they describe the most relevant clinical data involving each agent with regard to their safety profile and antineoplastic activity. Particular focus is given to the LUX-Lung 8 trial, which compared erlotinib and afatinib as a second-line treatment in a population of patients affected by advanced SCC of the lung.

Expert opinion

Despite being overcome by new therapeutic strategies – in particular immune checkpoint inhibitors – afatinib and erlotinib still represent potential treatment options down the line in lung SCC because they have a more manageable toxicity profile compared to chemotherapy.

KEYWORDS:

• Squamous-cell lung cancer
• tyrosine kinase inhibitors
• EGFR
• afatinib
• erlotinib

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Correction

Article highlights

• Activating mutations of EGFR are rarely found in squamous-cell lung cancer, but EGFR overexpression occurs in more than half cases.

• Erlotinib was approved as second- or further-line therapy for lung SCC, with an advantage in median OS of 2 months compared to placebo.

• Results from the LUX-Lung 8 trial defined a potential role of afatinib in the treatment of squamous-cell lung cancer.

• Recently, the approval of immune checkpoint inhibitors calls into question the role of second-line agents such as EGFR-TKIs in the treatment algorithm of lung SCC.

• EGFR-inhibitors represent a potential treatment option as further-line in squamous-cell lung cancer, albeit with an even more downsized role.

This box summarizes key points contained in the article.

Declaration of interest

F Grossi is on the advisory boards of and has received speaker’s grants from: Eli Lilly and Company, AstraZeneca, Merck Sharp and Dohme, Bristol-Myers Squibb and Pierre Fabre. C Genova has received speaker’s grants: from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme and Roche while E Rijavec has received a speaker’s grant from AstraZeneca. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.