Non-small cell lung cancer: an update on emerging EGFR-targeted therapies

ABSTRACT

Introduction

Current research in EGFR-mutated NSCLC focuses on the management of drug resistance and uncommon mutations, as well as on the opportunity to extend targeted therapies’ field of action to earlier stages of disease.

Areas covered

We conducted a review analyzing literature from the PubMed database with the aim to describe the current state of art in the management of EGFR-mutated NSCLC, but also to explore new strategies under investigation. To this purpose, we collected recruiting phase II-III trials registered on Clinicaltrials.govand conducted on EGFR-mutated NSCLC both in early and advanced stage.

Expert opinion

With this review, we want to provide an exhaustive overview of current and new potential treatments in EGFR-mutated NSCLC, with emphasis on the most promising newly investigated strategies, such as association therapies in the first-line setting involving EGFR-TKIs and chemotherapy (FLAURA2) or drugs targeting different driver pathways (MARIPOSA). We also aimed at unearthing challenges to achieve in this field, specifically the need to fully exploit already available compounds while developing new ones, the management of new emerging toxicities and the necessity to improve our biological understanding of the disease to design trials with a solid scientific rationale and to allow treatment personalization such in case of uncommon mutations.

KEYWORDS:

• EGFR
• non-small cell lung cancer
• osimertinib
• uncommon mutations
• resistance mechanisms

Article highlights

• EGFR-mutated NSCLC accounts for 10-15% of non-squamous NSCLC among Caucasian population and 50% among Asians.

• The approval of three generations of EGFR-TKIs throughout the years has led to a radical change in the quality of life and survival outcomes of patients affected by NSCLC harboring EGFR common mutations.

• Resistance occurs virtually in all patients and new treatment strategies, including new drugs development and combination therapies, are under evaluation.

• Targeting the rarer and variegated so-called “uncommon mutations”, including EGFR exon 20 insertions, represents a main challenge to achieve in the field of EGFR-mutated disease with recently presented positive results.

• The benefit of integrating TKIs into clinical practice since early-stage NSCLC have been recently demonstrated by the ADAURA trial and other peri-operative strategies are under evaluation.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.