Tagrisso-Chemo vs. Leclaza-Rybrevant: Competition Intensifies
AstraZeneca’s FLAURA2 Results Highlight Direct Head-to-Head Battle for First-Line EGFR-Mutant NSCLC
AstraZeneca has reported significant results for the combination of Tagrisso (osimertinib) with chemotherapy, directly challenging competition from the Leclaza (lazertinib) plus Rybrevant (amivantamab) regimen.
In two large Phase III trials in EGFR-mutant non-small cell lung cancer (NSCLC), both regimens delivered meaningful survival benefits compared with Tagrisso alone, underscoring an intensifying race in first-line treatment strategies.
On September 7, AstraZeneca presented final overall survival (OS) results from the FLAURA2 trial at the World Conference on Lung Cancer (WCLC 2025). The study compared Tagrisso monotherapy with Tagrisso plus chemotherapy. According to Dr. David Planchard of Gustave Roussy Cancer Institute, the combination achieved a median OS of 47.5 months, reducing the risk of death by 23% compared with monotherapy (37.6 months; HR=0.77, 95% CI 0.61–0.96, p=0.0202).
Progression-free survival (PFS) was also significantly improved, reaching 29.4 months versus 19.9 months with Tagrisso alone. Among patients with CNS metastases, median PFS was 24.9 months with combination therapy compared to 13.8 months in the monotherapy group.
At the European Lung Cancer Congress (ELCC) in March, researchers presented final OS data from the Phase III MARIPOSA trial, comparing Leclaza plus Rybrevant with Tagrisso monotherapy. At a median follow-up of 37.8 months, the Leclaza combination had not yet reached median OS, while Tagrisso showed 36.7 months. The Leclaza regimen reduced the risk of death by 25% (HR=0.75, 95% CI 0.61–0.92, p<0.005).
Although the two studies were not head-to-head, both Tagrisso plus chemotherapy and Leclaza plus Rybrevant reduced mortality risk by more than 20% versus Tagrisso alone, demonstrating broadly comparable survival advantages.
Until recently, Leclaza plus Rybrevant was the only regimen with a proven OS benefit in the first-line setting. With AstraZeneca’s new FLAURA2 data, both strategies now affirm a common conclusion: combination therapies outperform Tagrisso monotherapy in EGFR-mutant NSCLC.
In Korea, however, uptake will depend heavily on reimbursement policies. Since May, a partial reimbursement system has allowed oncology combinations to be prescribed as first-line treatments. While Tagrisso, Leclaza, and chemotherapy are covered, Rybrevant remains non-reimbursed, leaving patients to shoulder significant costs. How these new data will influence the adoption of the higher-priced Leclaza-Rybrevant regimen remains uncertain.