P08.04 Comparative Clinical Outcomes Between EGFR Exon20ins and Wildtype NSCLC Treated with Immune Checkpoint Inhibitors

Document Type

Conference Proceeding

Publication Date


Publication Title

J Thorac Oncol


Introduction: Mutation of the epidermal growth factor receptor (EGFR) is a major oncogenic driver in non-small cell lung cancer (NSCLC), and up to 12% of all EGFR-mutant NSCLCs harbor Exon 20 insertion mutations (Exon20ins). The insensitivity of Exon20ins to EGFR tyrosine kinase inhibitors has been well documented, but the activity of immune checkpoint inhibitors (ICIs) has not been closely examined due to the frequent exclusion of patients with EGFR mutations from large immunotherapy-based NSCLC trials.

Methods: We conducted a retrospective study to compare clinical outcomes of ICI-treated patients with EGFR Exon20ins and wildtype NSCLC (wt-NSCLC, defined as EGFR, ALK test negative). Patients with advanced NSCLC with non-squamous histology from the Flatiron Health database from 2015 to 2020 were included in this analysis. Real-world time to next therapy (rwTTNT) was the primary endpoint and analyzed using multivariable Cox proportional hazards model (covariates: age, time from advanced diagnosis to index date, time from initial to advanced diagnosis, sex, ECOG performance status, smoking history, and practice type) stratified by ICI initiation line of therapy. Overall survival was the secondary endpoint. Both endpoints were summarized by Kaplan-Meier method.

Results: Clinical outcomes of ICI therapy were assessed in 5365 with wt-NSCLC against 59 patients with Exon20ins NSCLC. ICI treatment was received as first or second-line therapy in 25% and 41% of Exon20ins and 39% and 42% of wt-NSCLC patients, respectively. The most common ICIs received by Exon20ins and wt-NSCLC patients were nivolumab (64% and 51%) and pembrolizumab (32% and 42%), respectively. Patients with Exon20ins had a 58% increased risk of shorter time to next-line therapy compared to wt-NSCLC (adjusted hazard ratio of 1.58 [95% CI, 1.2–2.1]; p=0.0012). The median rwTTNT was 3.7 months (95% CI, 3.0–4.9) for Exon20ins compared with 5.8 months (95% CI, 5.6–6.0) for wt-NSCLC (Figure). At 12-months, 10% of Exon20ins patients remained on ICIs compared with 31% of wt-NSCLC patients. No meaningful difference in survival between the Exon20ins and wt-NSCLC groups was observed.

Conclusion: ICI therapy was less effective for patients with Exon20ins compared with wt-NSCLC, although the sample size for Exon20ins NSCLC was smaller. The limited effectiveness of current treatment options for patients with EGFR Exon20ins NSCLC stress the need for new targeted therapies.





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