AURA3 shows no OS benefit of osimertinib vs chemotherapy
medwireNews: The phase 3 AURA3 trial has failed to demonstrate a significant overall survival (OS) gain with second-line osimertinib versus platinum–pemetrexed in patients with advanced non-small-cell lung cancer (NSCLC) carrying the EGFR T790M resistance mutation.
“The lack of survival benefit is possibly due to the high proportion of patients (73%) who crossed over from the platinum-pemetrexed arm to receive osimertinib,” comment Yi-Long Wu (Guangdong Lung Cancer Institute, Guangzhou, China) and co-investigators in the Annals of Oncology.
Previously the AURA3 study – comprising 419 patients who had progressed after treatment with one prior EGFR–tyrosine kinase inhibitor (TKI) – demonstrated significantly improved progression-free survival (PFS) and better central nervous system outcomes among the 279 patients who were randomly assigned to receive osimertinib 80 mg/day compared with the 140 who instead received up to six cycles of cisplatin or carboplatin alongside pemetrexed.
However, this PFS improvement did not translate into an OS benefit, say the researchers, who found that the median OS durations were 26.8 and 22.5 months for osimertinib- and chemotherapy-treated participants, respectively, giving a nonsignificant hazard ratio (HR) for death of 0.87.
In an exploratory analysis that adjusted for crossover, the median OS for the osimertinib group remained the same, but that for the chemotherapy group fell to 15.9 months, which equated to an HR of 0.54, albeit still without reaching statistical significance.
“The safety profile of osimertinib was consistent with the primary analysis, with no new safety signals,” report Wu and colleagues. The incidence of treatment-related adverse events (TRAEs) of at least grade 3 was lower in the osimertinib than chemotherapy arm, at 9% and 34%, respectively, as was the rate of discontinuation due to TRAEs, at 5% versus 9%. The corresponding rates were 9% and 1% among patients who crossed over to receive osimertinib.
The team highlights that “[t]he clinical implications of these results should be considered in light of data from the FLAURA trial,” which has shown a significant OS benefit with first-line osimertinib relative to comparator EGFR–TKIs.
Noting that there is currently “no way to confidently predict which patients who start first- or second-generation EGFR-TKIs will progress with T790M disease,” the researchers comment that “using osimertinib as first-line treatment provides more patients the opportunity to receive the associated OS benefit of osimertinib.”
Nevertheless, they conclude: “The continued tolerable safety profile reported here for osimertinib, together with superior PFS, improved patient quality of life and longer time to symptom deterioration versus platinum-pemetrexed, reinforces osimertinib as standard-of-care second-line treatment for patients with T790M advanced NSCLC and disease progression on a prior EGFR-TKI.”
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