A Real-World Study of Patients with Advanced Non-squamous Non-small Cell Lung Cancer with EGFR Exon 20 Insertion: Clinical Characteristics and Outcomes

Background In Europe, few data regarding the characteristics of EGFR exon 20 insertion (20ins) mutations in non-small cell lung cancer (NSCLC) are available. Objective Using a large real-world cohort, we assessed the incidence, characteristics, and outcomes of patients with non-squamous (nsq) NSCLC harboring EGFR exon 20ins. Patients and Methods The Epidemio-Strategy and Medical Economics advanced and metastatic lung cancer data platform including advanced/metastatic nsqNSCLC patients from January 2015 was analyzed (cut-off date: June 30, 2020). Characteristics, epidermal growth factor receptor ( EGFR ) mutation and other mutations, treatment patterns, and clinical outcomes were assessed for patients harboring EGFR exon 20ins, common EGFR mutations, other EGFR mutations, and wild-type EGFR . Survival parameters were estimated by the Kaplan-Meier method in these four groups. Results Out of 9435 nsqNSCLC patients tested for EGFR , 1549 (16.4%) had a mutation, including 61 with EGFR exon 20ins (3.9% of all mutated EGFR ). These 61 patients had a mean age of 63.6 years, were mostly female (68.9%) and non-smokers (55.7%), with de novo stage IV disease (73.8%) and performance status 0–1 (76.9%). Almost all patients (95.1%) with exon 20ins received systemic therapy (median, three lines). First-line systemic treatments consisted mainly of combination chemotherapy (70.7%), single-agent EGFR tyrosine kinase inhibitors (10.3%), and single-agent immunotherapy (5.2%). After a median follow-up of 25.0 (95% confidence interval [CI] 22.3–32.4) months, the median real-world overall survival was 24.3 (19.1–32.6) months in patients with exon 20ins compared to 35.4 (95% CI 32.6–37.5) in patients with common EGFR mutation ( n = 1049) ( p = 0.049) and 19.6 (95% CI 18.6–20.5) in patients with wild-type EGFR ( n = 7866) ( p = 0.2). Conclusions This large national study in nsqNSCLC patients confirms that EGFR exon 20ins is a rare condition (0.6%). The prognosis associated with exon 20ins appears to be in line with that of wild-type EGFR , but worse than common EGFR mutations, highlighting the need for advancements for this rare population.