Skip to main content

Osimertinib in Non-Small Cell Lung Cancer (NSCLC) with Atypical EGFR Activating Mutations: A Retrospective Multicenter Study

*January 2023*

Epidermal growth factor receptor (EGFR) mutations drive a subset of non-small cell lung cancer (NSCLC). Patients harboring the common EGFR mutations, deletion of exon 19 (Ex19del) and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. However, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations.

Patients from six US academic cancer centers were included with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent Ex19del, L858R, or T790M mutations. Baseline clinical characteristics were collected. The primary endpoint was the time to treatment discontinuation (TTD) of osimertinib. In evaluable patients, objective response rate (ORR) by RECIST 1.1 was assessed.

Fifty NSCLC patients with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n=18), G719X (28%, n=14), and Exon 20 insertion (14%, n=7). The median TTD of osimertinib was 9.7 months (95% CI, 6.5 – 12.9) overall and 10.7 months (95% CI, 3.2 – 18.1) in the first line setting (n=20). The ORR was 31.7% (95% CI, 18.1 – 48.1%) overall and 41.2% (95% CI, 18.4 – 67.1%) in the first line setting. The median TTD varied among patients with L861Q (17.2 months), G719X (7.8 months), and exon 20 insertion (1.5 months) mutations.

Osimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR activating mutation. Read more.