Activity of OsimeRTInib in NSCLC with Uncommon EGFR Mutations: Retrospective Observational Multicenter Study (ARTICUNO)

Introduction: Osimertinib is a third generation TKI representing the standard of care for treatment of metastatic NSCLC harboring classical EGFR mutations (exon 19 deletion and L858R). In 10-20% of patients with EGFR alterations, an assorted group of other uncommon mutations can also be detected. These mutations confer variable sensitivity to first- and second-generation TKIs, with overall lower therapeutic activity. Data of Osimertinib in this heterogenous group of mutations are limited and strongly warranted. Methods: This is a retrospective multicenter study of patients with advanced NSCLC with any uncommon alteration of EGFR and treated with Osimertinib since August 2017. Investigators collected response in terms of overall response rate (ORR) and disease control rate (DCR) by RECIST 1.1 criteria. Progression free survival (PFS), duration of response (DOR) and overall survival (OS) were estimated by Kaplan-Meier method. Results: As of February 2022, 50 patients with NSCLC with uncommon EGFR mutations were identified in 13 institutions in Italy. Patients’ characteristics: 64% female, median age 64 (32-87) years, 86% ECOG PS 0-1, 66% smoking history, 90% Caucasian, 94% adenocarcinoma. Most frequent sites of metastasis were lung (60%), bone (44%), and brain (30%). The most frequent mutations were compound mutations (30%, N=15), L861Q (20%, N=10), and G719X (14%, N=7) (Table 1). In 84% (n=42) Osimertinib was used in TKI-naïve setting and in 78% as first treatment. Median time of follow up was 11.5 months. ORR and DCR were 49% (CI 95%, 34-64%) and 85% (CI 95%, 72-94%) in the overall evaluable population (N=47), and 53% (CI 95%, 35-70%) and 84% (CI 95%, 67-94%) in TKI-naïve (excluded ins20) cohort, respectively. Highest responses were observed in cases with L861X, followed by G719X and compound mutations. Median PFS and DOR in TKI-naïve were 11 months (CI 95%, 6.3-15.7) and 14 months (CI 95%, 5-14), respectively. Notably, one patient with EGFR-KDD and one with D770_N771insSVD (ins20) achieved long-term responses. Conclusions: In this first analysis of 50 patients, the most frequent uncommon EGFR mutations were G719X, followed by L861X and S768I, largely occurring as compound, consistently with previously reported frequencies. Osimertinib showed activity with response in about half of patients, overall. Data from this first real-life Italian study appear comparable with those described in a prospective Korean phase 2 trial with Osimertinib and with those reported with Afatinib. ARTICUNO study is still ongoing and more updated data will be presented.