[HTML][HTML] Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC
SS Ramalingam, J Vansteenkiste… - … England Journal of …, 2020 - Mass Medical Soc
SS Ramalingam, J Vansteenkiste, D Planchard, BC Cho, JE Gray, Y Ohe, C Zhou…
New England Journal of Medicine, 2020•Mass Medical SocBackground Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the
epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI–
sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line
osimertinib with other EGFR-TKIs in patients with EGFR mutation–positive advanced non–
small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with
osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or …
epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI–
sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line
osimertinib with other EGFR-TKIs in patients with EGFR mutation–positive advanced non–
small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with
osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or …
Background
Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation–positive advanced non–small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported.
Methods
In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point.
Results
The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P=0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group.
Conclusions
Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.)
The New England Journal Of Medicine