The Role of Lazertinib in Patients With EGFR-Variant Non–Small Cell Lung Cancer
Mené sur 40 patients présentant des métastases cérébrales ayant pour origine un cancer du poumon non à petites cellules avec mutations EGFR (âge médian : 63 ans), cet essai non randomisé de phase II évalue l'efficacité, du point de vue du taux de réponse objective intracrânienne, et la toxicité du lazertinib (un inhibiteur de tyrosine kinase de l'EGFR de troisième génération) après l'échec d'un traitement par inhibiteur de tyrosine kinase de l'EGFR de première ou deuxième génération
The identification and targeting of EGFR variants (mutations) have significantly improved outcomes for a key molecular subtype of patients with non–small cell lung cancer (NSCLC). However, a high incidence of brain metastases is observed in EGFR-variant NSCLC, presenting serious clinical challenges, especially in patients who have failed prior EGFR tyrosine kinase inhibitors (EGFR-TKIs).Hong et al presented the outcomes of the KCSG LU phase 2 nonrandomized trial, focusing on the central nervous system (CNS) activity of lazertinib, a third-generation EGFR-TKI targeting common and T790M variants, in Korean patients with EGFR-variant NSCLC harboring brain metastases after failing first- or second-generation EGFR-TKIs. The study reported an overall intracranial objective response rate (ORR) of 55.3% and a median intracranial progression-free survival (PFS) of 15.8 months, with a cerebrospinal fluid penetration rate of 46.2%. These results highlight lazertinib’s efficacy in the CNS. Interestingly, the study reported a disparity between intracranial and extracranial responses to lazertinib, with the extracranial ORR being significantly lower at 18.4%. The authors speculated that pharmacokinetic resistance might contribute to this lower extracranial ORR, although further research is needed to validate this hypothesis.