The FLAURA2 trial is a phase III trial comparing single agent osimertinib or osimertinib with platinum-based chemotherapy as first-line therapy for patients with advanced EGFR mutant lung cancer.
What was the study design?
It was a 1:1 randomisation to single agent osimertinib or in combination with platinum-based chemotherapy where patients would be treated with four cycles of combination platinum pemetrexed followed by pemetrexed and osimertinib maintenance therapy.
What results were you presenting?
We knew from prior studies or prior presentations that the combination improved both progression free survival and overall survival compared to single agent osimertinib. In the presentation at ESMO 2025 I presented the outcome in patients with poor prognostic clinical or molecular features. So the clinical features included brain metastases, liver metastases, bone metastases. In all three cases, whether or not patients had one of those poor prognostic features, the combination of osimertinib and chemotherapy led to an improvement in overall survival compared to osimertinib alone. The differences were more pronounced in patients who had one of those poor clinical prognostic features compared to if they did not.
Similarly, we looked at three different molecular features – the specific EGFR mutation, either exon 19 deletion or L858R; presence of concomitant TP53 mutations in the tumour; and then circulating tumour DNA at diagnosis where EGFR mutation was detectable. Similar to the clinical features, in all cases whether or not patients had one of those, their cancer had one of those poor molecular features, the combination of osimertinib and platinum pemetrexed led to a better or longer overall survival compared to osimertinib alone. The differences were more pronounced in patients whose cancers had one of those molecular features compared to if they did not.
So, overall, the presentation helped to reinforce that regardless of presence or absence of poor prognostic clinical or molecular features osimertinib and platinum pemetrexed is a superior therapy compared to osimertinib and leads to an overall improvement in survival.
What were the adverse events?
Of course combination therapy had more adverse events which mostly came from the addition of the two treatments together. So adding chemotherapy to a well-tolerated targeted therapy like osimertinib led to more chemotherapy-like side effects, so nausea, vomiting and hematologic toxicities as well as fatigue. There were no new side effects that emerged when the two therapies were combined together and the combination did not lead to a greater incidence of interstitial pneumonitis than is seen typically with osimertinib which is, in and of itself, quite low but it didn’t make that low number higher.
