Osimertinib alone

A phase III, multicenter, randomized, double-blind, controlled trial (FLAURA [NCT02296125]) compared osimertinib, an oral, third-generation, irreversible EGFR TKI that inhibits both EGFR-TKI–sensitizing variants and the EGFR T790M resistance variant, with standard of care EGFR TKIs (gefitinib or erlotinib) as first-line treatment of patients with previously untreated, EGFR-positive (exon 19 deletion or L858R), advanced NSCLC, as detected by a U.S. Food and Drug Administration (FDA)-approved test.[49] The 556 patients were randomly assigned in a 1:1 ratio.

A phase III, multicenter, randomized, double-blind, controlled trial (FLAURA [NCT02296125]) compared osimertinib, an oral, third-generation, irreversible EGFR TKI that inhibits both EGFR-TKI–sensitizing variants and the EGFR T790M resistance variant, with standard of care EGFR TKIs (gefitinib or erlotinib) as first-line treatment of patients with previously untreated, EGFR-positive (exon 19 deletion or L858R), advanced NSCLC, as detected by a U.S. Food and Drug Administration (FDA)-approved test.[49] The 556 patients were randomly assigned in a 1:1 ratio.

The primary end point of PFS was significantly longer with osimertinib (18.9 months vs. 10.2 months; HR, 0.46; 95% CI, 0.37–0.57, P < .001).[49][Level of evidence B1]

A phase III, multicenter, randomized, double-blind, controlled trial (FLAURA [NCT02296125]) compared osimertinib, an oral, third-generation, irreversible EGFR TKI that inhibits both EGFR-TKI–sensitizing variants and the EGFR T790M resistance variant, with standard of care EGFR TKIs (gefitinib or erlotinib) as first-line treatment of patients with previously untreated, EGFR-positive (exon 19 deletion or L858R), advanced NSCLC, as detected by a U.S. Food and Drug Administration (FDA)-approved test.[49] The 556 patients were randomly assigned in a 1:1 ratio.

The objective response rate was similar for both groups (80% for the osimertinib group vs. 76% for the standard EGFR TKI group).

A phase III, multicenter, randomized, double-blind, controlled trial (FLAURA [NCT02296125]) compared osimertinib, an oral, third-generation, irreversible EGFR TKI that inhibits both EGFR-TKI–sensitizing variants and the EGFR T790M resistance variant, with standard of care EGFR TKIs (gefitinib or erlotinib) as first-line treatment of patients with previously untreated, EGFR-positive (exon 19 deletion or L858R), advanced NSCLC, as detected by a U.S. Food and Drug Administration (FDA)-approved test.[49] The 556 patients were randomly assigned in a 1:1 ratio.

Central nervous system (CNS) progression was observed less often in the osimertinib group compared with the standard EGFR TKI group (6% vs. 15%).

A phase III, multicenter, randomized, double-blind, controlled trial (FLAURA [NCT02296125]) compared osimertinib, an oral, third-generation, irreversible EGFR TKI that inhibits both EGFR-TKI–sensitizing variants and the EGFR T790M resistance variant, with standard of care EGFR TKIs (gefitinib or erlotinib) as first-line treatment of patients with previously untreated, EGFR-positive (exon 19 deletion or L858R), advanced NSCLC, as detected by a U.S. Food and Drug Administration (FDA)-approved test.[49] The 556 patients were randomly assigned in a 1:1 ratio.

The median duration of response (DOR) was 17.2 months (95% CI, 13.8–22.0) with osimertinib versus 8.5 months (95% CI, 7.3–9.8) with standard EGFR TKIs.

A phase III, multicenter, randomized, double-blind, controlled trial (FLAURA [NCT02296125]) compared osimertinib, an oral, third-generation, irreversible EGFR TKI that inhibits both EGFR-TKI–sensitizing variants and the EGFR T790M resistance variant, with standard of care EGFR TKIs (gefitinib or erlotinib) as first-line treatment of patients with previously untreated, EGFR-positive (exon 19 deletion or L858R), advanced NSCLC, as detected by a U.S. Food and Drug Administration (FDA)-approved test.[49] The 556 patients were randomly assigned in a 1:1 ratio.

OS was a key secondary end point. With a follow-up of at least 39 months in each group, the median OS was 38.6 months (95% CI, 34.5–41.8) in the osimertinib group and 31.8 months (95% CI, 26.6–36.0) in the standard EGFR TKI group (HRdeath 0.80; 95.05% CI, 0.64–1.00; P = .046).[50][Level of evidence A1]

A phase III, multicenter, randomized, double-blind, controlled trial (FLAURA [NCT02296125]) compared osimertinib, an oral, third-generation, irreversible EGFR TKI that inhibits both EGFR-TKI–sensitizing variants and the EGFR T790M resistance variant, with standard of care EGFR TKIs (gefitinib or erlotinib) as first-line treatment of patients with previously untreated, EGFR-positive (exon 19 deletion or L858R), advanced NSCLC, as detected by a U.S. Food and Drug Administration (FDA)-approved test.[49] The 556 patients were randomly assigned in a 1:1 ratio.

The crossover rate from the standard EGFR TKI group to the osimertinib group was 31% (85 of 277) among patients assigned to the standard EGFR TKI group and 47% (85 of 180) among patients discontinuing the EGFR TKI. The authors noted that this crossover probably contributed to the duration of OS in the EGFR TKI (31.8 months).

A phase III, multicenter, randomized, double-blind, controlled trial (FLAURA [NCT02296125]) compared osimertinib, an oral, third-generation, irreversible EGFR TKI that inhibits both EGFR-TKI–sensitizing variants and the EGFR T790M resistance variant, with standard of care EGFR TKIs (gefitinib or erlotinib) as first-line treatment of patients with previously untreated, EGFR-positive (exon 19 deletion or L858R), advanced NSCLC, as detected by a U.S. Food and Drug Administration (FDA)-approved test.[49] The 556 patients were randomly assigned in a 1:1 ratio.

No new safety signals were observed. Rates of adverse events of grade 3 or higher and adverse events leading treatment discontinuations were similar between groups. Adverse events leading to dose interruptions, reductions, or permanent discontinuations were 43%, 5%, and 15%, respectively, in the osimertinib group and 41%, 4%, and 18%, respectively, in the EGFR TKI group.