Dr Jänne on an Exploratory Analysis from FLAURA2 of Baseline ctDNA in EGFR+ NSCLC

Pasi A. Jänne, MD, PhD, senior physician, senior vice president for translational medicine, director, Belfer Center for Applied Cancer Science, director, Chen-Huang Center for EGFR Mutant Lung Cancers, David M. Livingston, MD, Chair, Dana-Farber Cancer Institute, professor of medicine, Harvard Medical School, discusses findings from an exploratory analysis of the phase 3 FLAURA2 trial (NCT04035486), which examined baseline and on-treatment EGFR mutation dynamics in plasma for patients with EGFR-mutant non–small cell lung cancer (NSCLC) treated during the study.

Previously reported clinical data from FLAURA2 supported the February 2024 FDA approval of osimertinib (Tagrisso) plus platinum-based chemotherapy for the treatment of patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations. Investigators conducted the exploratory analysis to examine the correlation between EGFR mutations detected in plasma at baseline per circulating tumor DNA (ctDNA) and progression-free survival (PFS).

Findings from the exploratory analysis presented at the 2024 AACR Annual Meeting showed that in patients who were treated with osimertinib plus chemotherapy or osimertinib alone who did not have EGFR mutations in plasma detected via ctDNA at baseline (n = 113) experienced a median PFS of 30.5 months (95% CI, 25.0-not calculable) compared with 18.3 months (95% CI, 15.4-21.0) for those who did have EGFR mutations in plasma per ctDNA (n = 308; HR, 0.55; 95% CI, 0.42-0.73). Jänne notes that a PFS benefit was observed in patients who did not have baseline plasma EGFR mutations in both the osimertinib/chemotherapy arm (HR, 0.64; 95% CI, 0.42-0.98) and the osimertinib monotherapy arm (HR, 0.51; 95% CI, 0.35-0.76).

Notably, patients with baseline EGFR mutations in plasma experienced a PFS benefit when treated with osimertinib plus chemotherapy vs osimertinib alone (HR, 0.60; 95% CI, 0.45-0.80); however, the PFS outcomes were similar between the two arms for patients who did not have EGFRmutations in plasma at baseline (HR, 0.93; 95% CI, 0.51-1.72).

Jänne also explains that the clearance of EGFR mutations in plasma at weeks 3 and 6 was similar between the two arms. Patients who experienced clearance of these mutations from their ctDNA at week 3 experienced improvements in PFS compared with those with persistent EGFR mutations in plasma, irrespective of treatment arm, he continues. However, regardless of whether patients experienced ctDNA clearance, the addition of chemotherapy to osimertinib provided a PFS benefit vs osimertinib alone, Jänne concludes.