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. 2025 Oct 17.
doi: 10.1056/NEJMoa2510308. Online ahead of print.

Survival with Osimertinib plus Chemotherapy in EGFR-Mutated Advanced NSCLC

Pasi A Jänne  1 , David Planchard  2   3 , Kunihiko Kobayashi  4 , James Chih-Hsin Yang  5   6 , Ying Liu  7 , Natalia Valdiviezo  8 , Tae Min Kim  9 , Liyan Jiang  10 , Hiroshi Kagamu  4 , Noriko Yanagitani  11 , Jialei Wang  12 , Bivas Biswas  13 , Artem Poltoratskiy  14 , Yeni Neron  15 , Carlos Rojas  16 , Leona Koubkova  17 , Carles Escriu  18 , Doreen A Ezeife  19 , Helen Mann  20 , Elena Armenteros-Monterroso  21 , Yuri Rukazenkov  22 , Chee Khoon Lee  23 ; FLAURA2 Investigators
Affiliations

Survival with Osimertinib plus Chemotherapy in EGFR-Mutated Advanced NSCLC

Pasi A Jänne et al. N Engl J Med. .

Abstract

Background: The primary analysis of this trial showed that first-line treatment with osimertinib plus chemotherapy with a platinum-based agent and pemetrexed led to significantly longer progression-free survival than osimertinib monotherapy among patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC). Results from the planned final analysis of overall survival are needed.

Methods: In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced NSCLC who had not previously received treatment for advanced disease to receive either osimertinib (80 mg once daily) plus chemotherapy with pemetrexed (500 mg per square meter of body-surface area) and a platinum-based agent (cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or osimertinib monotherapy (80 mg once daily). The key secondary end point was overall survival.

Results: A total of 557 patients were randomly assigned to the osimertinib plus platinum-pemetrexed group (279 patients) or the osimertinib monotherapy group (278 patients). The median overall survival was 47.5 months in the osimertinib plus platinum-pemetrexed group and 37.6 months in the osimertinib monotherapy group (hazard ratio for death, 0.77; 95% confidence interval, 0.61 to 0.96; P = 0.02). Grade 3 or higher adverse events of any cause were reported in 70% of the patients in the osimertinib plus platinum-pemetrexed group and in 34% of the patients in the osimertinib monotherapy group; adverse events leading to the discontinuation of osimertinib were reported in 12% and 7%, respectively.

Conclusions: Among patients with EGFR-mutated advanced NSCLC, first-line treatment with osimertinib plus platinum-pemetrexed led to significantly longer overall survival than osimertinib monotherapy and was associated with an increased risk of reversible adverse events of grade 3 or higher. (Funded by AstraZeneca; FLAURA2 ClinicalTrials.gov number, NCT04035486.).

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