Role of Osimertinib in the Treatment of EGFR-Mutation Positive Non-Small-Cell Lung Cancer

Abstract

Mutations in the EGFR occur in approximately 10–35% of non-small-cell lung cancer (NSCLC) patients. Osimertinib is a third-generation oral small molecule inhibitor of EGFR, active against the common targetable activating EGFR mutations in L858R and exon 19 deletion; it also inhibits the T790M mutation. It was initially developed and approved for the treatment of acquired resistance to EGFR inhibition mediated by the T790M pathway activation. Recently, the FLAURA trial showed significantly improved progression-free survival with osimertinib compared with the first generation EGFR tyrosine kinase inhibitors gefitinib or erlotinib; this has led to its approval by US FDA and European Medicines Agency (EMA) as frontline therapy. Ongoing studies will define the resistance mechanisms to osimertinib, novel combination approaches and role in earlier stages of NSCLC.

Keywords::

• acquired resistance
• AZD9291
• EGFR
• non-small-cell lung cancer
• osimertinib
• T790M
• tyrosine kinase inhibitor

Financial&competing interests disclosure

S Ramalingam has consulting or advisory roles with Amgen, Boehringer Ingelheim, Celgene, Genentech/Roche, Lilly/ImClone, Bristol-Myers Squibb, AstraZeneca, Abbvie, Merck, Takeda, Tesaro; receives institutional research funding from Abbvie, ER Squibb&Sons, Pfizer, Merck, AstraZeneca, Vertex Pharmaceuticals, Takeda, EMB Serono; and receives funding for travel, accommodations and expenses from EMD Serono, Pfizer, AstraZeneca, Amgen, ER Squibb&Sons, Abbvie, Lilly and Merck. 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.

No writing assistance was utilized in the production of this manuscript.