Osimertinib in Patients With Non–Small Cell Lung Cancer and Uncommon EGFR Mutations—Chasing Unicorns?
Mené sur 40 patients atteints d'un cancer du poumon non à petites cellules présentant des mutations inhabituelles au niveau des gènes EGFR (âge médian : 72 ans ; durée de suivi : 6 mois), cet essai non randomisé de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'osimertinib en traitement de première ligne
The identification of genomic alterations within driver oncogenes has revolutionized the management of non–small cell lung cancer (NSCLC). Indeed, we now approach the twentieth anniversary of the discovery of epidermal growth factor receptor (EGFR) mutations in NSCLC, a finding that catalyzed a new paradigm of precision medicine that has culminated in regulatory approvals of more than 20 targeted agents across various oncogenes. Importantly, insights into EGFR-mutant biology have continued to provide a roadmap for management of oncogene-driven NSCLC. Historically, EGFR-mutant NSCLC has been classified into 3 distinct subgroups. Classic EGFR mutations, which are characterized by exon 19 deletions or the exon 21 L858R substitution, account for approximately 80% of EGFR mutations and confer marked sensitivity to EGFR tyrosine kinase inhibitors. By contrast, EGFR exon 20 insertion mutations, which compose approximately 10% of EGFR mutations, are generally insensitive to treatment with early-generation EGFR inhibitors. Finally, uncommon or atypical EGFR mutations comprise a heterogeneous group of point mutations, deletions, or insertions within exons 18 to 25 and make up the remaining 10% to 15% of EGFR mutations. Currently, the optimal management of patients with these atypical mutations remains an open question. Okuma and colleagues present findings from the UNICORN study, a prospective, multicenter, phase 2 trial aimed at evaluating the clinical activity of the third-generation EGFR inhibitor osimertinib in patients with NSCLC harboring uncommon EGFR mutations. Among 42 treatment-naive patients enrolled over a 2-year period, the objective response rate (ORR) was 55% with a median progression-free survival (PFS) of 9.4 months. The median duration of response was 22.7 months. Consistent with earlier studies using osimertinib, common adverse events included diarrhea (47.5%), acneiform eruption/rash (42.5%), thrombocytopenia (65%), and mucositis (32.5%), but only 3 patients (7.5%) required dose reductions.
JAMA Oncology 2024