EGFR-mutated NSCLC: Osimertinib data updates
The latest data from the FLAURA2 and NorthStar trials provide additional guidance on the use of osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC).
The findings presented at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany, focused on outcomes in patients with baseline predictors of poor prognosis and on the merits of local consolidative therapy (LCT) in oligometastatic disease.
Pasi Jänne (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) reported exploratory analyses of the phase 3 FLAURA2 study, which was previously presented at WCLC 2025 and is now published in The New England Journal of Medicine. He reminded the audience of the primary results, which showed significant increases in progression-free survival (PFS) and overall survival (OS) with osimertinib plus chemotherapy over osimertinib monotherapy.
In the FLAURA2 exploratory analyses, the OS benefit with osimertinib plus chemotherapy was consistently observed regardless of baseline prognostic factors
Jänne explained that the team assessed OS according to central nervous system metastases, L858R mutation, detectable plasma EGFR-mutated ctDNA, liver metastases, bone metastases, and altered tissue TP53. Although not statistically significant in these subgroup analyses, the hazard ratios for OS all favored osimertinib plus chemotherapy over osimertinib monotherapy, ranging from 0.70 to 0.83.
The presenter said that this “further reinforc[es] this as a first-line standard of care in EGFR-mutated NSCLC.”
Invited discussant, Christine Lovly (Vanderbilt University Medical Center, Nashville, Tennessee, USA), commented that such features have the potential to determine which patients benefit most from treatment intensification.
For patients with oligometastatic disease, eliminating residual disease that has resistant clones has been shown to be generally effective, but what about the EGFR-mutated setting?
Yasir Elamin (University of Texas, Houston, USA) presented the results of the phase 2 randomized study NorthStar, which addressed this question, investigating osimertinib with or without LCT for metastatic EGFR-mutated NSCLC.
There was a significant difference in median PFS, at 25.3 months with osimertinib plus LCT (n=56) versus 17.5 months with osimertinib alone (n=63).
Elamin reported “early separation of the curves,” which was maintained at year 3 with a PFS rate of 40% in the LCT group versus 24% in the osimertinib-only group. This benefit was observed across disease burden groups, including polymetastatic disease.
There was no excess toxicity with the addition of LCT, and there was not an increased rate of pneumonitis above that expected with thoracic radiation.
Zofia Piotrowska (Massachusetts General Hospital Cancer Center, Boston, USA) commented that, while NorthStar met its primary endpoint with improved PFS, “as we seek to apply these data to our clinical practice, many questions remain.”
She cautioned that the heterogeneity of participants and the delivered treatments may limit generalizability, noting that “patient selection and timing will be key.”
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