Evaluating entrectinib as a treatment option for non-small cell lung cancer

ABSTRACT

Introduction

Entrectinib, an oral pan-TRK, ALK, and ROS1 inhibitor is approved as a first-line treatment for NTRK-rearranged solid tumors and ROS1-rearranged non-small cell lung cancer (NSCLC). It has demonstrated clinical efficacy for patients harboring the relevant gene rearrangement in both systemic and intracranial disease, regardless of the tumor type.

Areas covered

In this review, the authors analyzed data from preclinical and clinical studies, the characteristics of entrectinib compared to those of other relevant inhibitors (currently available and/or under investigation), and the emerging resistance mechanisms. The authors then provide the readers with their future perspectives.

Expert opinion

Entrectinib has been well studied across many tumor types, including NSCLC with ALK, ROS1, and NTRK rearrangements. The drug has demonstrated favorable properties with oral administration, prolonged response duration, high intracranial efficacy, and a favorable toxicity profile. However, with acquisition of resistance and the development of newer generation TKIs, the optimal place for entrectinib in the landscape of targeted therapies for NSCLC warrants further validation.

KEYWORDS:

• ALK
• entrectinib
• non-small cell lung cancer
• NTRK
• ROS1

Article Highlights

• Entrectinib is an oral pan-TRK, ALK, and ROS1 inhibitor that has demonstrated its clinical efficacy in clinical trials.

• Its strength lies in oral administration, prolonged response duration, high intracranial efficacy, and favorable toxicity profiles.

• It is a viable therapeutic option for TKI-naïve advanced NSCLC patients harboring ROS1 or NTRK gene rearrangements.

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

One referee declares that have an advisory role for Pfizer and Takeda and has also worked on entrectininb and repotrectinib trials. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.