Patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC) lived almost twice as long without disease progression after initial treatment with an EGFR inhibitor compared with standard of care tyrosine kinase inhibitor (TKI) therapy.
EGFR TKIs are considered standard of care for first-line treatment of EGFR-positive NSCLC because of prior research demonstrating a boost in progression-free survival (PFS) of about 10 months. However, more than 50% of patients treated with first- and second-generation EGFR TKIs develop resistance to therapy through a T790M mutation. Osimertinib is a third-generation EGFR inhibitor that inhibits T790M resistance mutations and has activity in the central nervous system.
Suresh Ramalingam, MD, Emory University Winship Cancer Institute (Atlanta, GA), and colleagues conducted a study to determine the effectiveness of osimertinib vs standard EGFR TKIs as initial treatment in advanced NSCLC. A total of 556 patients were randomized to receive either therapy. Eligible patients exhibited pathology-confirmed Exon 19 deletion/L858R mutations, had no prior EGFR TKI treatment, and were neurologically stable with brain metastases.
The primary endpoint of the trial was PFS, and secondary endpoints included response rate, duration of response, disease control rate, and overall survival (OS), among others. Results of the trial were presented at the 2017 European Society for Medical Oncology conference (September 8-12, 2017; Madrid, Spain).
Researchers reported that initial treatment with osimertinib led to a median PFS of 18.9 months, compared with 10.2 months for patients who received standard-of-care. Additionally, patients in the osimertinib group benefited from a 54% reduction in the hazard for disease progression or death (95% CI, 0.37-0.57; P < .0001).
Median survival was reportedly not reached in either group. Objective response rate (ORR) was calculated at 80% in the osimertinib group, compared with 76% in the standard-of-care group. Despite this similar outcome, the duration or response was more than doubled in the osimertinib group (17.2 months vs 8.5 months, respectively).
Furthermore, researchers reported that adverse event rates were comparable between the treatment groups, though osimertinib was associated with fewer grade ≥ 3 events and a lower discontinuation rate.
Investigators concluded that osimertinib demonstrated a superior benefit over standard of care as first-line therapy in patients with advanced EGFR-positive NSCLC. These findings support frontline use of osimertinib in EGFR-mutated disease, they wrote.—Zachary Bessette