FLAURA: First-Line OS Benefit Confirmed For Advanced EGFR-Mutated NSCLC

medwireNews: Updated FLAURA trial results have been reported at the ESMO Congress 2019, confirming the superiority of osimertinib for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an activating epidermal growth factor receptor (EGFR) mutation. 

“The final OS [overall survival] analysis of FLAURA reinforces osimertinib as the standard-of-care for first-line treatment of patients with [EGFR-mutated] advanced NSCLC”, Suresh Ramalingam, from Emory University in Atlanta, Georgia, USA, told delegates at the meeting in Barcelona, Spain. 

Earlier results from FLAURA demonstrated an improvement in progression-free survival (PFS) with the third-generation EGFR–tyrosine kinase inhibitor (TKI) compared with gefitinib or erlotinib in tumours with an exon 19 deletion or L858R mutation. 

In this final analysis, median OS was 38.6 months for the 279 patients who were randomly assigned to receive osimertinib 80 mg/day versus 31.8 months for the 277 given gefitinib 250 mg/day or erlotinib 150 mg/day, with a significant hazard ratio (HR) for death of 0.799. 

However, subgroup analysis indicated the OS benefit with osimertinib was only significant for non-Asian patients (HR=0.542) and not their Asian counterparts.  

Osimertinib was associated with longer median duration of treatment than comparator EGFR–TKI, at 20.7 versus 11.5 months, with 70%, 42% and 28% of patients remaining on treatment at 12, 24 and 36 months, respectively, compared with 47%, 16% and 9% of those given the comparator EGFR–TKI. 

And time to first subsequent therapy was also significantly longer with osimertinib, at 25.5 months versus 13.7 months with the comparator agent (HR=0.478). Of note, almost a third (31%) of patients who began on gefitinib or erlotinib crossed over to osimertinib therapy, the presenter said. 

Safety analysis showed a lower rate of grade 3 or more severe adverse events with osimertinib than the comparator agents (18 vs 29%) despite the greater exposure to treatment. 

Speaking to medwireNews, Suresh Ramalingam summarised that “osimertinib has a very good tolerability profile that allows patients to experience improvement in survival without a detrimental effect on quality of life.” 

He concluded: “Giving the best drug first is the preferred approach for treating patients with advanced-stage lung cancer and the FLAURA results confirm the superiority of osimertinib in this setting.”

Reference  

Ramalingam RS, Gray JE, Ohe Y, et al. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): final overall survival analysis. ESMO Congress 2019; Barcelona, Spain: 27 September–1 October. LBA5_PR