Osimertinib Is Still Standard First-Line Treatment for NSCLC With EGFR Mutation

New YorkAt the 23rd Annual Perspectives in Thoracic Oncology meeting, Charu Aggarwal, MD, MPH, Assistant Professor of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, discussed the use of targeted EGFR tyrosine kinase inhibitors (TKIs) in the front-line setting for patients with EGFR-positive NSCLC.

“Targeted therapy in this day and age has been consistently shown to improve survival,” she stated.

“We have been able to dissect different subtypes of NSCLC, and we are beginning to really appreciate the biology that drives survival, that drives prognosis, and we can actually predict how patients will do,” she added.

EGFR mutation testing is currently considered the standard of care in the front-line setting after diagnosis of nonsquamous non-small-cell lung cancer.

Dr Aggarwal explained that there are several randomized studies that have established oral TKI as a superior therapy compared with chemotherapy for this patient population. There are currently 5 FDA-approved oral TKIsdacomitinib, erlotinib, gefitinib, afatinib, and osimertinib.

Osimertinib remains the standard approach for first line therapy in EGFR-mutated NSCLC. Dr Aggarwal highlighted the FLAURA trial enrolled patients with locally advanced or metastatic NSCLC. Patients were stratified by mutation status and randomized 1:1 to osimertinib or either gefitinib or erlotinib. Patients receiving osimertinib had a progression free survival of 18.9 months versus 10.2 months in patients receiving gefitinib or erlotinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001).  

Dacomitinib, recently approved by the FDA, appears promising as first-line therapy in this patient population, but may not be relevant given the toxicity and availability of osimertinib. Dr Aggarwal discussed the phase 3 ARCHER trial, which evaluated dacomitinib as an alternative first-line treatment for patients who have advanced NSCLC with EGFR mutation.

Patients were randomized in a 1:1 ratio to receive dacomitinib or gefitinib. Patients who received dacomitinib had a median progression-free survival of 14.3 months versus 9.5 months in the group receiving gefitinib. However, 66% of patients receiving dacomitinib required dose reduction compared with 8% of patients receiving gefitinib.

In addition to these data, there is emerging evidence suggesting that the combination with chemotherapy may prolong progression-free survival and overall survival; however, studies are still ongoing.

Throughout her presentation, Dr Aggarwal highlighted that among drugs approved for this patient population, osimertinib remains the standard approach for the first-line therapy. Dacomitinib appears promising, but may not be relevant, she told listeners.

“A significant percentage of these patients never make it to second-line therapy, so we really should offer the safest, most effective approach at first,” Dr Aggarwal concluded.Janelle Bradley

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