FLAURA Trial: Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC

First-line treatment with osimertinib in patients with EGFR-mutated is associated with longer overall survival compared with other drugs in its class.

Osimertinib is a third-generation, irreversible oral EGFR tyrosine kinase inhibitor (TKI) that selectively inhibits EGFR-TKI–sensitizing and EGFR T790M–resistance mutations. FLAURA was a double-blind, randomized phase 3 trial that compared first-line osimertinib with other EGFR-TKIs in patients with advanced non–small-cell lung cancer (NSCLC) and EGFR mutation. In the primary analysis (cutoff, June 12, 2017), osimertinib showed superior progression-free survival compared with the comparator regimen (gefitinib or erlotinib). The researchers reported the final analysis of overall survival (OS).

A total of 556 patients with previously untreated NSCLC with an EGFR mutation were randomized to osimertinib 80 mg once daily (N = 279) or comparator EGFR-TKIs (N = 277), which included gefitinib 250 mg once daily (N = 183) or erlotinib 150 mg once daily (N = 94) until disease progression, unacceptable toxicity, or withdrawal of consent. Comparator group patients were allowed to cross over to receive osimertinib following independently confirmed disease progression; documentation of the presence of a T790M-resistance mutation was required.

At 3 years, 28% of patients in the osimertinib group and 9% of patients in the comparator group continued to receive a trial regimen. At data cutoff, the median duration of treatment was 20.7 months with osimertinib and 11.5 months in the comparator group. The median duration of follow-up for OS was 35.8 months in the osimertinib group and 27 months in the comparator group. More patients achieved OS in the osimertinib group versus the comparator group at 12 months (89% vs 83%), 24 months (74% vs 59%), and 36 months (54% vs 44%). The median OS was 38.6 months (95% confidence interval [CI], 34.5-41.8 months) in the osimertinib group versus 31.8 months (95% CI, 26.6-36.0 months) in the comparator group (hazard ratio for death, 0.80; P = .046). According to the researchers, crossover from the comparator group to the osimertinib group likely contributed to the 31.8-month duration of OS in the comparator group.

Despite a longer duration of treatment with osimertinib versus the comparator regimens, the safety profiles were similar across treatment groups. Grade ≥3 adverse events (AEs) were more common in the comparator group compared with the osimertinib group (47% vs 42%). In both groups, 27% of patients reported serious AEs. In the osimertinib group, 3% of patients experienced fatal AEs (none were deemed treatment-related). In the comparator group, 4% of patients experienced fatal AEs (2 were deemed treatment-related). Similar percentages of patients in the osimertinib and comparator groups reported AEs leading to dose reductions (5% and 4%, respectively) and treatment discontinuations (15% and 18%, respectively). The most common AEs of any grade in the osimertinib and comparator groups were diarrhea (60% and 58%, respectively) and rash/acne (59% and 79%, respectively).

The researchers concluded that osimertinib was associated with significantly longer OS versus comparator EGFR-TKIs and had a similar safety profile in treatment-naïve patients with EGFR mutation–positive, locally advanced or metastatic NSCLC.

Reference
Ramalingam SS, et al. N Engl J Med. 2020;382:41-50.