AACR 2024 | FLAURA2: EGFRm dynamics in NSCLC treated with osimertinib

So in this analysis, we evaluated the baseline presence of EGFR mutations in circulating tumor DNA and how that changed over during the course of treatment in the FLAURA2 randomized clinical trial. The trial evaluated patients with advanced EGFR mutant lung cancer and were randomized to osimertinib alone or to the combination of osimertinib and platinum based chemotherapy. What the study showed was that, a fair proportion of patients had ctDNA detected at baseline, and the outcome of those patients in general was similar to the outcome of the entire population of the larger trial, and that chemo addition of chemotherapy improved the progression free survival compared to osimertinib alone. Patients who had detectable ctDNA at baseline, regardless of their treatment, had a worse prognosis than patients who had non-detectable ctDNA at their baseline. And that was true for osimertinib alone or osimertinib and chemotherapy.

If you look at patients who had detectable ctDNA at baseline when they got the combination therapy, they did better than osimertinib alone if they had no detectable ctDNA at baseline. The outcomes in terms of progression free survival were actually fairly similar between osimertinib alone and the combination, although the combination was a little bit better. We subsequently evaluated changes over time. We know that clearance of ctDNA is a prognostic factor. And we saw that, uh, independent of the arm in about 80% of patients, we could detect ctDNA clearance patients who cleared their ctDNA either with osimertinib alone or osimertinib and chemotherapy had a better prolonged progression free survival. These findings are consistent with the larger literature at large, suggesting that detection of ctDNA at baseline is a poor prognostic feature, and that clearance of ctDNA leads to a prolonged improvement in progression free survival. So it’s nice to see this in the context of the randomized clinical trial. There’s a suggestion that maybe patients with baseline detectable ctDNA do better than when treated with a combination compared to osimertinib alone, although that was true in the entire patient population as well.

So I think we need to continue to study the evolution of ctDNA. And how do we end up using that moving forward? There are trials where patients ongoing, where patients start with osimertinib, and if they don’t clear their ctDNA, then, uh, patients are randomized to continue osimertinib. Or the combination of osimertinib and chemotherapy. And I think that will help answer the question of does intensification during the course of therapy rescue that poor prognostic, uh, feature? What we’re showing here is that when you get chemotherapy and osimertinib from the beginning, that’s better than osimertinib alone in terms of PFS and and overall outcome of patients.