First-line treatment with osimertinib prolonged PFS compared with standard epidermal growth factor receptor tyrosine kinase inhibitors among patients with EGFR-mutated non-small cell lung cancer, according to results of the double-blind, phase 3 FLAURA study published in The New England Journal of Medicine.
Osimertinib (Tagrisso, AstraZeneca) — an oral, third-generation, irreversible EGFR TKI that selectively inhibits EGFR TKI-sensitizing and EGFR T790M resistance mutations — also demonstrated a similar safety profile as, but a lower rate of serious adverse events than, standard treatments.
Based on results from the AURA trial, osimertinib is approved for the treatment of patients with EGFR T790M-mutated NSCLC who have progressed during or after EGFR TKI therapy. Data from that trial, along with preclinical data, suggested osimertinib also may be an effective first-line treatment.
Jean-Charles Soria, MD, PhD, professor of medicine and medical oncology at South-Paris University, and colleagues of the FLAURA study randomly assigned 556 patients with previously untreated, EGFR-mutation positive advanced NSCLC 1:1 to 80 mg osimertinib once daily or a standard EGFR TKI. Standard treatments included 250 mg gefitinib (Iressa, AstraZeneca) once daily or 150 mg erlotinib (Tarceva; Genentech, Astellas Oncology) once daily.
Investigator-assessed PFS served as the study’s primary endpoint.
Median duration of total treatment exposure at the time of data cutoff was 16.2 months (range, 0.1-27.4) among patients assigned osimertinib and 11.5 months (range, 0-26.2) among patients assigned a standard EGFR TKI.
Progression or death occurred in 136 patients (49%) in the osimertinib group and 206 (74%) in the standard group.
Researchers reported significantly longer median PFS among patients in the osimertinib group (18.9 months vs. 10.2 months; HR = 0.46; 95% CI, 0.37-0.57).
A similar proportion of patients in both arms achieved an objective response to treatment (80% vs. 76%; OR = 1.27; 95% CI, 0.85-1.9). However, median duration of response was 17.2 months (95% CI, 13.8-22) with osimertinib and 8.5 months (95% CI, 7.3-9.8) with standard EGFR TKIs.
OS data were only 25% mature at the time of the analysis. Eighty-three percent (95% CI, 78-87) of patients assigned osimertinib achieved 18-month OS compared with 71% (95% CI, 65-76) of patients assigned standard treatment (HR = 0.63; 95% CI, 0.45-0.88), but these data did not meet the P value of .0015 for statistical significance at interim analysis.
Fewer patients assigned osimertinib experienced grade 3 or worse adverse events (34% vs. 45%).
The most common adverse events included rash or acne (osimertinib, 58%; standard EGFR TKI, 78%), diarrhea (58%; 57%) and dry skin (36% for both).
“Although there was no statistical comparison of safety data, the safety profile of osimertinib was similar to that of standard EGFR TKIs, but with somewhat lower rates of adverse events of grade 3 or higher, despite a longer median duration of exposure with osimertinib,” Soria and colleagues wrote. “These data suggest that osimertinib is superior to current standard EGFR TKIs as first-line therapy.” – by Alexandra Todak
Disclosures: AstraZeneca funded this study. Soria reports personal fees from AstraZeneca and Roche during the conduct of the study. Please see the full study for a list of all other authors’ relevant financial disclosures.