Activity of OsimeRTInib in NSCLC with UNcommon EGFR Mutations: Retrospective observational multicenter study (ARTICUNO)

Background In 10-20% of patients (pts) with EGFR mutated NSCLC, an assorted group of uncommon mutations can be detected. These mutations confer variable sensitivity to 1st and 2nd generation TKIs, overall resulting in lower therapeutic activity. Data of Osimertinib (Osi), a 3rd generation TKI, are limited and strongly warranted. Methods This is a retrospective multicenter study of pts with advanced NSCLC with any uncommon EGFR alteration and treated with Osi since August 2017. Investigators collected response in terms of overall response rate (ORR) and disease control rate (DCR) by RECIST 1.1 criteria. Survival outcomes were estimated by Kaplan-Meier method. Results As of April, 2022, 65 pts were identified in 18 institutions in Italy. Pts characteristics: 62% female, median age 68 (31-87) years, 86% ECOG PS 0-1, 63% smoking history, 92% caucasian, 95% adenocarcinoma. A large group of pts presented compound mutations (37%, N=24) (Table). In 88% (N=57) Osi was used in TKI-naïve setting and in 80% as first treatment. ORR and DCR were 45% (CI 95%, 32-58%) and 78% (CI 95%, 66-88%) in the evaluable population (N=60), and 49% (CI 95%, 34-64%) and 78% (CI 95%, 63-88%) in TKI-naïve (excluded ins20) cohort (N=49), respectively. With a median time of follow up of 13 months, median PFS and DOR in TKI-naïve were 11 months (CI 95%, 7-18) and not reached (CI 95%,11-n.r.), respectively. Conclusions In this widest known dataset, major uncommon mutations were the most frequent, largely occurring as compound. Notably, one third of our cases presented heterogeneous minor uncommon mutations. Osimertinib showed relevant activity, overall comparable with data of Afatinib and Osi in a Korean trial. ARTICUNO study is still ongoing and more data will be presented.