Osimertinib improves OS in untreated, advanced NSCLC
First-line osimertinib improved OS compared with standard-of-care epidermal growth factor receptor tyrosine kinase inhibitors among patients with previously untreated advanced EGFR-mutated non-small cell lung cancer, according to results from the randomized phase 3 FLAURA trial presented at European Society for Medical Oncology Asia Congress and simultaneously published in The New England Journal of Medicine.
“[This] phase 3 trial compared first-line osimertinib with other EGFR TKIs in patients with EGFR mutation-positive advanced NSCLC,” Suresh S. Ramalingam, MD, FASCO, deputy director of Winship Cancer Institute of Emory University, and colleagues wrote. “The trial showed longer PFS with osimertinib compared with the comparator EGFR TKIs (HR for disease progression or death = 0.46). Data from the final analysis of OS have not been reported.”
In the current study, Ramalingam and colleagues reported the planned final OS analysis.
Researchers randomly assigned 556 patients with previously untreated NSCLC with an EGFR mutation in a 1:1 fashion to 80 mg once-daily osimertinib (Tagrisso, AstraZeneca; n = 279) — a third-generation, irreversible oral EGFR TKI that selectively inhibits EGFR TKI-sensitizing and EGFR T790M-resistance mutations — or to comparator EGFR TKIs (n = 277), which included 250 mg once-daily gefitinib (Iressa, AstraZeneca) or 150 mg once-daily erlotinib.
Median follow-up for the entire population was 43 months; median follow-up for OS was 35.8 months in the osimertinib group and 27 months in the comparator group.
At 3 years, 28% of patients assigned osimertinib and 9% of patients assigned the comparator TKIs remained on treatment. Median exposure to treatment was 20.7 months in the osimertinib group vs. 11.5 months in the comparator group.
Results showed a median OS of 38.6 months (95% CI, 34.5-41.8) with osimertinib compared with 31.8 months (95% CI, 26.6-36) in the comparator group (HR = 0.8; 95.05% CI, 0.64-1).
A greater proportion of patients achieved OS in the osimertinib group at 12 months (89% vs. 83%), 24 months (74% vs. 59%) and 36 months (54% vs. 44%).
Grade 3 or higher adverse events appeared more common among those assigned the comparator TKIs (47% vs. 42%). Twenty-seven percent of patients in each group experienced serious adverse events, and nine patients (3%) assigned osimertinib and 10 (4%) assigned comparator TKIs experienced fatal adverse events.
“The safety profile for osimertinib was similar to that of the comparator EGFR TKIs, despite a longer duration of exposure in the osimertinib arm,” the researchers wrote. – by Jennifer Southall
Disclosures: The study was funded by AstraZeneca. Ramalingam reports grants or personal fees from Advaxis, AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo Oncology, Nektar, Takeda and Tesaro outside of the study. Please see the study for all other authors’ relevant financial disclosures.