The treatment of advanced lung adenocarcinoma with activating EGFR mutations

ABSTRACT

Introduction

Lung adenocarcinomas account for approximately 40–50% of all NSCLC (Non-Small Cell Lung Cancer) cases. In addition, lung adenocarcinomas can harbor several different genetic mutations, EGFR (Epidermal Growth Factor Receptor) being the most frequent one, accounting for approximately 5–15% of all the mutations in western patients and for approximately 40–55% in Asian patients; on the other hand, EGFR mutations are uncommon in squamous histology. Approximately 90% of EGFR mutations are represented by exon 19 in-frame deletion and by the L858R exon 21-point mutation, that confer sensitivity to EGFR TKI (Tyrosine Kinase Inhibitors) treatment.

Areas covered

The authors comprehensively review the current state of the art with reference to EGFR+ NSCLC treatment and to discuss the possible future developments.

Expert opinion

Osimertinib must be considered the preferred first-line agent in EGFR+ advanced NSCLC patients thanks to its superior performances. With respect to acquired resistance mechanisms to osimertinib, the currently ongoing clinical trials will surely help us to better understand and tackle them. Globally, we strongly believe that a biomarker-driven sequential treatment algorithm is key in order to provide personalized, effective and durable therapies in the increasingly complex landscape of EGFR+ advanced NSCLC.

KEYWORDS:

• NSCLC
• EGFR
• Osimertinib
• Resistance Mechanisms
• Treatment algorithms
• C797X
• MET amplification

Article highlights

• EGFR mutations in lung adenocarcinoma account for approximately 5–15% of all the mutations in western patients and for approximately 40–55% in Asian patients

• As of today, five EGFR-TKI are FDA and EMA-approved for the first-line treatment of advanced EGFR+ NSCLC patients with exon 19 deletion or exon 21 L858R mutation: erlotinib, gefitinib, afatinib, dacomitinib and osimertinib

• There is no common ground on the issue of the preferred first-line drug between the main oncology organizations

• The data coming from the FLAURA study clearly establish osimertinib as the best treatment for naïve patients, thanks to its superior performances

• There is little to no data available with respect to post-upfront osimertinib progression. A biomarker-driven sequential treatment algorithm is key in order to provide personalized, effective and durable therapies in this setting.

Declaration of interest

C Gridelli has received honoraria for speaker bureau service and as an advisory board member from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme and Roche. 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.