FLAURA findings add to evidence for CNS efficacy of osimertinib in advanced NSCLC
medwireNews: Osimertinib treatment is associated with a reduced risk for central nervous system (CNS) progression relative to erlotinib or gefitinib in patients with epidermal growth factor receptor (EGFR)-mutated, advanced non-small-cell lung cancer (NSCLC) and brain metastases, trial results suggest.
The phase III FLAURA trial – comprising 556 treatment-naïve patients with locally advanced or metastatic NSCLC and asymptomatic or stable CNS metastases – previously showed significantly better progression-free survival (PFS) with osimertinib, a third-generation EGFR inhibitor, than with the first-generation agents. The incidence of CNS progression in the overall trial population was also lower with osimertinib, say Johan Vansteenkiste (University Hospital KU Leuven, Belgium) and co-authors.
For the current prespecified analysis, they focused on the 128 participants with measurable or nonmeasurable CNS lesions, finding that median PFS as evaluated by blinded independent review was not reached for the osimertinib-treated patients and was 13.9 months for those given erlotinib or gefitinib.
This equated to a hazard ratio of 0.48, which could only be classed as “nominally significant” due to the trial design, which did not allow for a formal analysis of the CNS PFS as the overall survival analysis had not reached statistical significance, the investigators explain. They believe, however, that osimertinib therapy is associated with a “clinically meaningful” improvement in CNS outcomes.
A higher proportion of patients in the osimertinib than in the control group achieved a CNS objective response (66 vs 43%; odds ratio=2.5), while the incidence of CNS progression was lower (20 vs 39%) as was the rate of CNS progression due to new lesions (12 vs 30%).
Moreover, Vansteenkiste et al used a competing risks analysis adjusting for non-CNS progression and death to estimate that osimertinib-treated patients had a 5% probability of experiencing a CNS event at 6 months and an 8% probability at 12 months. By contrast, the estimates for patients given erlotinib or gefitinib were 18% and 24%, respectively.
“Taken together, the consistent CNS efficacy observed across analyses in the FLAURA study, assessed by investigator in the overall FLAURA population and by [blinded independent central review] in the CNS analysis, provides strong evidence for the CNS efficacy of osimertinib,” concludes the team in the Journal of Clinical Oncology.
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