Algorithme thérapeutique en 2025 des cancers bronchiques non à petites cellules avec mutation de l'EGFR

Abstract

EGFR mutations remain the most frequently observed targetable oncogenic driver in non-small cell lung cancer (NSCLC), accounting for 12% of adenocarcinomas and 44% of NSCLC cases in non-smokers in France. The «common» EGFR mutations—exon 19 deletions and the exon 21 L858R mutation—are found in 89% of cases. The use of new molecular biology techniques has led to the identification of «rare» EGFR mutations, particularly exon 20 insertions, and has also revealed molecular heterogeneity both at diagnosis and during follow-up. This heterogeneity partly explains the variability in the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) and contributes to the emergence of resistant clones. Osimertinib has been the standard first-line therapy for several years. However, the role of combined chemotherapy and the emergence of amivantamab—a bispecific EGFR-MET antibody—are changing the landscape of first-line treatment options, whether in combination or not, as well as the sequencing of therapies, with the goal of improving overall survival.

These advances, however, come with increased toxicities and a risk of impaired quality of life, underscoring the need to carefully select patients who are most likely to benefit from each therapeutic option. Finally, the indications for osimertinib are expanding, with its use now approved in the adjuvant post-surgical setting and its anticipated arrival in neoadjuvant (pre-operative) and consolidation therapy after chemoradiation for patients with localized or locally advanced unresectable NSCLC.