An overview of osimertinib as a treatment of non-small cell lung cancer (NSCLC): an update

ABSTRACT

Introduction: Osimertinib is a third-generation anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), that irreversibly binds to mutant EGFR, specifically to the T790M EGFR mutant non-small cell lung cancer (NSCLC). Since its approval, osimertinib has been tested in multiple scenarios, including the first-line and adjuvant setting of EGFR-mutant disease.

Areas covered: The authors summarize the most recent evidence about osimertinib in NSCLC, covering its use as a first-line therapy, its activity on central nervous system metastatic disease, and in elderly patients. Moreover, the authors focus on resistance to this drug and on the therapeutic strategies that may be used to overcome this issue.

Expert opinion: Osimertinib is a key player in the treatment ofEGFR mutant NSCLC and will probably be used in earlier clinical settings in the future, giving rise to an emerging variety of resistance mechanisms. These could be potentially overcome in several ways: e.g. as an oligo-progressive disease local therapy, maintaining osimertinib might be a reasonable option; however, for widespread progressive disease, a switch to chemotherapy should be considered. Finally, either liquid biopsy or tissue biopsy might be considered in patients progressing to osimertinib, as they can lead to the identification of potentially targetable resistance mechanisms.

KEYWORDS:

• Non-small cell lung cancer
• EGFR
• osimertinib
• acquired resistance
• tyrosine kinase inhibitor

Article highlights

• Osimertinib is currently the standard of care for patients with advanced, EGFR-mutant NSCLC.

• Osimertinib is active in multiple patient sub-populations, including elderly patients, patients with central nervous system metastases and Asian patients, provided that EGFR mutation is detected.

• Currently, the optimal post-progression approach to patients who received osimertinib is yet to be elucidated; while several clinical trials with targeted agents based on acquired resistance mechanisms are being conducted, real-world patients still receive chemotherapy.

• Based on the recent data from ADAURA trial, osimertinib is likely to become the standard therapeutic approach to EGFR-mutant NSCLC in the adjuvant setting.

Declaration of interest

C Genova has received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, and Roche. Furthermore, D Planchard has received honoraria from Peer CME and Prime Onoclogy. He has also served as an advisor or as a consultant to AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Medimmune, MSD Oncology, Novartis, Pfizer, and Roche. He has also received funding via his institution from AstraZeneca/Medimmune, AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, Merck & Co, Novartis, Pfizer, Roche, Sanofi, and Taiho Pharmaceutical Co. Ltd. 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

One referee declares receiving honoraria from AstraZeneca. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.