FLAURA2 –⁠ a step forward in first-line treatment of advanced EGFR-mutated non-small cell lung cancer

Czech version

Authors: MUDr. Ján Podhorec; prof. MUDr. Alexandr Poprach, Ph.D.
Authors‘ workplace: Klinika komplexní onkologické péče LF MU a MOÚ, Brno
Published in: Klin Onkol 2026; 39(5): 325-330
Category: Review
doi: https://doi.org/10.48095/ccko2026325

Overview

Background: Activating mutations in epidermal growth factor receptor (EGFR) represent one of the most important therapeutically targetable alterations in advanced non-small cell lung cancer (NSCLC). Osimertinib has become a first-line standard of care due to its efficacy, favorable safety profile, and activity in the central nervous system. Nevertheless, most patients eventually experience disease progression during treatment, and searching for strategies that further prolong disease control and delay the emergence of resistance remains an important clinical need. The FLAURA2 study evaluated the combination of osimertinib with platinum-based chemotherapy and pemetrexed in previously untreated patients with locally advanced or metastatic EGFR-mutated non-squamous NSCLC. Compared with osimertinib monotherapy, combination treatment demonstrated a significant prolongation of progression-free survival, and in the final analysis, also a statistically significant improvement in overall survival, with a median of 47.5 months vs. 37.6 months (HR for death 0.77; 95% CI 0.61–0.96; P = 0.02). Aim: The aim of this review article is to summarize the FLAURA2 study and its main clinically relevant results in patients with advanced EGFR-mutated NSCLC treated in the first-line setting. The text describes the study design, characteristics of the study population, and treatment arms, focusing on the efficacy outcomes of osimertinib combined with platinum-pemetrexed chemotherapy compared with osimertinib monotherapy, particularly in terms of progression--free survival, overall survival, and intracranial efficacy. The review also includes a summary of the safety profile of the combination treatment and the main conclusions of the published analyses of the study.

Keywords:

Drug therapy – carcinoma – non-small-cell lung cancer – osimertinib – combination – epidermal growth factor receptor (EGFR) – FLAURA2

Sources

1. Reungwetwattana T, Nakagawa K, Cho BC et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small--cell lung cancer. J Clin Oncol 2018; 36 (33): 3290–3297. doi: 10.1200/JCO.2018.78.3118.

2. Ramalingam SS, Vansteenkiste J, Planchard D et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 2020; 382 (1): 41–50. doi: 10.1056/NEJMoa1913662.

3. Soria JC, Ohe Y, Vansteenkiste J et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018; 378 (2): 113–125. doi: 10.1056/NEJMoa1713137.

4. Noronha V, Patil VM, Joshi A et al. Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in EGFR-mutated lung cancer. J Clin Oncol 2020; 38 (2): 124–136. doi: 10.1200/JCO.19.01154.

5. Hosomi Y, Morita S, Sugawara S et al. Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study. J Clin Oncol 2020; 38 (2): 115–123. doi: 10.1200/JCO.19.01488.

6. Miyauchi E, Morita S, Nakamura A et al. Updated analysis of NEJ009: gefitinib-alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated EGFR. J Clin Oncol 2022; 40 (31): 3587–3592. doi: 10.1200/JCO.21.02911.

7. Saito R, Sugawara S, Ko R et al. Phase 2 study of osimertinib in combination with platinum and pemetrexed in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer: the OPAL study. Eur J Cancer 2023; 185 : 83–93. doi: 10.1016/j.ejca.2023.02.023.

8. Nakamura A, Saito R, Ko R et al. A phase II study of osimertinib in combination with platinum plus pemetrexed in patients with EGFR-mutated, advanced non-small cell lung cancer: the OPAL study (NEJ032C/LOGIK1801). J Clin Oncol 2022; 40 (16 Suppl): 9097. doi: 10.1200/JCO.2022.40.16_suppl.9097.

9. Planchard D, Feng PH, Karaseva N et al. Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study. ESMO Open 2021; 6 (5): 100271. doi: 10.1016/j.esmoop.2021.100271.

10. Planchard D, Jänne PA, Cheng Y et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med 2023; 389 (21): 1935–1948. doi: 10.1056/NEJMoa2306434.

11. Jänne PA, Planchard D, Kobayashi K et al. Survival with osimertinib plus chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med 2026; 394 (1): 27–38. doi: 10.1056/NEJMoa2510308.

12. Rangachari D, Yamaguchi N, VanderLaan PA et al. Brain metastases in patients with EGFR-mutated or ALK-rear-ranged non-small-cell lung cancers. Lung Cancer 2015; 88 (1): 108–111. doi: 10.1016/j.lungcan.2015.01.020.

13. Jänne PA, Planchard D, Kobayashi K et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer. J Clin Oncol 2024; 42 (7): 808–820. doi: 10.1200/JCO.23.02219.

14. Cho BC, Lu S, Felip E et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med 2024; 391 (16): 1486–1498. doi: 10.1056/NEJMoa2403614.

15. Yang JC, Lu S, Hayashi H et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med 2025; 393 (17): 1681–1693. doi: 10.1056/NEJMoa2503001.