KEY TAKEAWAYS
- The FLAURA2 phase III trial aimed to explore resistance mechanisms in osimertinib ± CT-treated EGFRm NSCLC patients.
- The result demonstrated that early osimertinib resistance in EGFRm NSCLC mirrors prior data, with CT not affecting subsequent targeted therapies.
Osimertinib (osi) is the go-to treatment for advanced EGFR-mutated nonsmall cell lung cancer(NSCLC), but resistance always emerges. The FLAURA2 trial compared osimertinib alone to adding chemo (CT) in this setting. Before full testing, a safety run-in checked the combo’s tolerability. For this study, researchers aimed to explore resistance mechanisms in osimertinib ± CT-treated EGFRm NSCLC patients.
Patients with previously untreated, EGFRm advanced NSCLC were treated with osi combined with CT (osi 80 mg once daily [QD] + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 or carboplatin AUC5 every Q3W for 4 cycles, followed by osi 80 mg QD + pemetrexed 500 mg/m2 Q3W) or osi monotherapy (80 mg QD) until disease progression or discontinuation criteria were met. Plasma circulating tumor DNA (ctDNA) samples were collected at baseline and at the time of disease progression and were analyzed using next-generation sequencing (Guardant Health, GuardantOMNI™).
Of 138 matched baseline and progression disease (PD) plasma samples analyzed, (10 from the SRI [osi + CT] and 128 from the randomized part [osi + CT, n=51; osi, n=77]). Among these, 126 had detectable EGFRm ctDNA at baseline (osi + CT, n=53; osi, n=73). Resistance mechanisms were generally comparable between treatment arms, with numerically fewer patients showing acquired EGFR C797S and MET amplification in the osi + CT arm compared to osi monotherapy. No novel resistance mechanisms were identified in patients receiving osi combined with chemotherapy.
The result demonstrated that early osimertinib resistance in EGFRm NSCLC mirrors prior data, with CT not affecting subsequent targeted therapies.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/45
Clinical Trial: https://clinicaltrials.gov/study/NCT04035486
Zhou C, Tang K, Liu B, Kim SW, Kitazono S, Ono A, Thiagarajan M, Hung JY, Boyer M, Xie J, Bhattacharya A, Baig M, Agrawal T, Knoblauch RE, Cho BC. Acquired mechanisms of resistance to first-line (1L) osimertinib with or without platinum-based chemotherapy (CT) in EGFR-mutated (EGFRm) advanced NSCLC: Preliminary data from FLAURA2. Presented at ESMO Asia Congress 2023; Abstract 514MO.
