Efficacy
First-line setting
FLAURA trialr
At time of data cut-off and interim analysis, the median duration of follow up was 15.0 months for progression-free survival and 9.7 months for survival for all patients. Median duration of total treatment exposure was 16.2 months for patients receiving osimertinib, and 11.5 months for those receiving standard EGFR-TKI. Results of the trial found the median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P = 0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs.
In the FLAURA trial after a median follow up of 43 months, the median OS was 38.6 months (95% CI, 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) (hazard ratio for death 0.80; 95.05% CI, 0.64 to 1.00; P=0.046) in the standard EGFR-TKI group.r
Health related quality of life reported improvements were statistically significant favouring the osimertinib group for emotional and social functioning. Cognitive functioning remained stable with osimertinib but deteriorated with erlotinib/gefitinib. Reported odds of improvement and time to deterioration of symptoms was similar in both groups.r
Kaplan-Meier Estimates for Progression Free Survival According to Treatment Groupr
© N Engl J Med 2018
Kaplan-Meier Estimates for Overall Survivalr
© N Engl J Med 2020
Second-line setting
AURA3 trialr
At the time of data cutoff, and interim analysis, the median follow-up for all patients was 8.3 months, and the median duration of treatment was 8.6 months in the osimertinib group and 4.8 months in the platinum-pemetrexed group. The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; hazard ratio; 0.30; 95% confidence interval [CI], 0.23 to 0.41; P<0.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24 to 40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001). Among 144 patients with metastases to the central nervous system (CNS), the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; hazard ratio, 0.32; 95% CI, 0.21 to 0.49).
Kaplan-Meier Estimates for Progression Free Survival According to Treatment Groupr
© N Engl J Med 2017