First-line therapy with osimertinib significantly prolongs overall survival of patients with non-small-cell lung carcinoma (NSCLC) compared to older tyrosine kinase inhibitors. This was shown by the evaluation of survival data from the FLAURA study, which included patients with Ex19del/L858R-EGFR-mutated advanced NSCLC.
The results were presented by Suresh S. Ramalingam, Winship Cancer Institute of Emory University, Atlanta, at the Presidential Symposium of the ESMO Congress 2019 in Barcelona.
FLAURA was a double-blind Phase 3 study in which patients with advanced NSCLC who had EGFR Exon 19 deletion or L858R mutation that had not received systemic treatment were enrolled. The efficacy and tolerability of osimertinib (80mg/day) (n = 279) and of a standard therapy were randomized and compared with gefitinib (250mg/day) or erlotinib (150mg/day) (n = 277). The primary endpoint was met, and osimertinib prolonged progression-free survival (PFS) from 10.2 months to 18.9 months (HR 0.46, p < 0.001).
Ramalingam presented the results of the secondary endpoint of overall survival (OS), the analysis of which was planned after the occurrence of about 318 deaths.
Patients treated with osimertinib lived a median of 38.6 months, and patients in the control group 31.8 months (HR 0.799, p = 0.0462). More than half of the patients (54%) still lived after three years in the osimertinib group, compared to 44% in the comparison group. The effect on OS could be seen in most subgroups, only people from the Asian region and patients with EGFR-L858R mutations did not benefit from osimertinib compared to standard tyrosine kinase inhibitors (TKIs).
In the osimertinib group, the median time was 25.5 months until the patients were treated with further therapy, in the comparison group 13.7 months (HR 0.478, p < 0.0001). Of the patients in the comparison group, 31% received osimertinib as the first subsequent treatment.
"The FLAURA study showed a statistically significant and clinically significant improvement in OS with osimertinib, and the OS was extended by 6.8 months," concluded Ramalingam. This was the first time that a TKI could be shown to prolong survival in patients with lung cancer compared to another TKI. "This final FLAURA OS analysis supports the role of osimertinib as a standard of care for patients with EGFR-mutated advanced NSCLC."
Discussant Pasi A. Jänne, MD from the Dana Farber Cancer Institute, Boston, described the results as clinically significant with an extension of median OS by 7 months. The effect was consistently detectable in the subgroups but varied in individual cases. These results changed clinical practice. For example, clinical practice in the USA has already changed accordingly. He no longer considers sequence therapy with EGFR tyrosine kinase inhibitors appropriate.
Ramalingam SS. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. ESMO 2019 Annual Meeting, 27. September bis 1. Oktober 2019, Barcelona, LBA5.