Afatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: An Updated Database of 1023 Cases Brief Report

<jats:sec><jats:title>Introduction</jats:title><jats:p>Previously, we developed a database of 693 patients with NSCLC and uncommon <jats:italic>EGFR</jats:italic> mutations treated with afatinib. Here, we provide an update of &gt;1000 patients, with more data on specific mutations.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients were identified from a prospective database developed by Boehringer Ingelheim and <jats:italic>via</jats:italic> literature review. Mutations were categorized as T790M-positive, exon 20 insertions, major uncommon (G719X, L861Q, S768I) and ‘others’. Patients with compound mutations (≥2 <jats:italic>EGFR</jats:italic> mutations) were analyzed separately. Key endpoints were time to treatment failure (TTF) and objective response rate (ORR).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of 1023 patients included, 587 patients were EGFR TKI-naïve and 425 were EGFR TKI-pretreated. The distribution of mutation categories was: major uncommon (41.4%); exon 20 insertions (22.3%); T790M (20.3%); and ‘others’ (15.9%); 38.6% had compound mutations. Overall, median TTF (TKI naïve/pretreated) was 10.7 and 4.5 months. ORR was 49.8% and 26.8%, respectively. In TKI-naïve patients, afatinib demonstrated activity against major uncommon mutations (median TTF: 12.6 months; ORR: 59.0%), ‘other’ mutations (median TTF: 10.7 months; ORR: 63.9%) including strong activity against E709X (11.4 months; 84.6%) and L747X (14.7 months; 80.0%), and compound mutations (11.5 months; 63.9%). Although sample sizes were small, notable activity was observed against specific exon 20 insertions at residues A763, M766, N771, and V769, and against osimertinib resistance mutations (G724S, L718X, C797S).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Afatinib should be considered as a first-line treatment option for NSCLC patients with major uncommon, compound, ‘other’ (including E709X and L747X) and some specific exon 20 insertion mutations. Moderate activity was seen against osimertinib resistance <jats:italic>EGFR</jats:italic> mutations.</jats:p></jats:sec>