FLAURA: First-line osimertinib improves post-progression outcomes in advanced NSCLC
The first-line use of osimertinib in patients with EGFR mutation–positive advanced non-small-cell lung cancer (NSCLC) is associated with significant improvements in a number of post-progression endpoints compared with current standard of care (SoC), according to new data from the phase III FLAURA study.
Previously reported results of the study showed significantly improved progression-free survival (PFS) with osimertinib vs gefitinib or erlotinib (median, 18.9 months vs 10.2 months; hazard ratio [HR], 0.46; p<0.001) in treatment-naïve patients with EGFR mutation–positive locally advanced or metastatic NSCLC (n=556). Interim overall survival (OS) data also favoured osimertinib, although the difference vs SoC EGFR tyrosine kinase inhibitor (TKI) therapy was not statistically significant (18-month OS rate, 83 percent vs 71 percent; HR, 0.63; p=0.007). [N Engl J Med 2018;378:113-125]
New data, presented at the European Lung Cancer Congress (ELCC) 2018, showed significantly longer time to first subsequent therapy (TFST) or death in patients on osimertinib vs those on SoC EGFR TKI (median, 23.5 months vs 13.8 months; HR, 0.51; p<0.0001). The median time to discontinuation of study treatment or death was 20.8 months in the osimertinib arm vs 11.5 months in the SoC EGFR TKI arm. [Planchard D, et al, ELCC 2018, abstract 128O]
At the time of data cut-off (12 June 2017), 49 percent of patients in the osimertinib arm and 77 percent of patients in the SoC EGFR TKI arm had discontinued study treatment. First subsequent therapy was received by 29 percent vs 47 percent of patients, with 10 percent vs 35 percent of patients receiving EGFR TKI–containing therapy (20 percent treated with subsequent osimertinib) and 16 percent vs 10 percent of patients receiving platinum-containing regimens.
“Second progression or death occurred in 26 percent of patients in the osimertinib arm vs 38 percent of those in the SoC EGFR TKI arm. The median time from randomization to second progression on subsequent treatment [PFS2] was not calculable in the osimertinib arm and was 20 months in the SoC EGFR TKI arm [HR, 0.58; p=0.0004],” reported Professor David Planchard of the Institut Gustave Roussy in Villejuif, France.
“Twenty-seven percent of patients in the osimertinib arm and 40 percent of patients in the SoC EGFR TKI arm started second subsequent therapy or died. The median time to second subsequent therapy [TSST] or death was not calculable with osimertinib and was 25.9 months with SoC EGFR TKI [HR, 0.60; p=0.0005],” he continued.
In both treatment arms, patients reported similar improvements in key symptoms, such as cough, dyspnoea, chest pain, appetite loss and fatigue, from baseline until discontinuation of randomized treatment. “However, clinically relevant improvement [ie, improvement of ≥10 points on a scoring range of 0–100] was seen only for cough in the osimertinib arm [-10.14 points vs -8.18 points for SoC EGFR TKI; p=0.180],” reported Dr Natasha Leighl of the Princess Margaret Hospital in Toronto, Canada. [Leighl N, et al, ELCC 2018, abstract 139PD]
“With the exception of chest pain [-6.84 for osimertinib vs -3.88 for SoC EGFR TKI; p=0.021], there were no significant differences between osimertinib and SoC EGFR TKI in patient-reported quality-of-life outcomes,” she added.