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Updated: Aug 29, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Comparative Clinical Outcomes Between EGFR Ex20ins and Wildtype NSCLC Treated with Immune Checkpoint Inhibitors
Nicolas Girard1, Anna Minchom2, Sai-Hong Ignatius Ou3
1Institut Curie, Institut du Thorax Curie-Montsouris, Paris, France.
Introduction:
The activity of immune checkpoint inhibitors (ICIs) in NSCLC harboring EGFR exon 20 insertion mutations (ex20ins) has not been closely examined due to the frequent exclusion of patients with EGFR mutations from large immunotherapy-based NSCLC trials.
Patients And Methods:
A real-world, retrospective study was conducted to compare outcomes of ICI-treated patients with EGFR ex20ins and wildtype NSCLC (wt-NSCLC; defined as EGFR and ALK test negative). Patients with advanced NSCLC from the Flatiron Health database (2015-2020) were included in the analysis. Real-world time to next therapy (rwTTNT) and overall survival (rwOS), stratified by ICI initiation line of therapy, were the prespecified primary and secondary endpoints, respectively.
Results:
Among 59 patients with EGFR ex20ins NSCLC and 5365 with wt-NSCLC, ICI treatment was received as first-line therapy in 25% and 39%, respectively. Patients with EGFR ex20ins had a 58% increased risk of shorter time to next-line therapy compared with wt-NSCLC (adjusted hazard ratio of 1.58 [95% confidence interval [CI], 1.2-2.1]; P = .0012). The median rwTTNT for first ICI line was 3.7 months (95% CI, 3.0-4.9) for EGFR ex20ins NSCLC compared with 5.8 months (95% CI, 5.6-6.0) for wt-NSCLC. No meaningful difference in rwOS between the groups was observed.
Conclusions:
ICI therapy may be less effective for patients with EGFR ex20ins compared with wt-NSCLC. Consistent with prior data on exon 19 deletion and L858R substitution, tumors harboring ex20ins appear to be less responsive to immune checkpoint inhibition than wt-NSCLC.
Insights
Immune checkpoint inhibitors (ICIs) show reduced effectiveness in non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions (ex20ins) compared to wildtype NSCLC. Patients with EGFR ex20ins experienced a significantly shorter time to next therapy.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) are a key treatment for non-small cell lung cancer (NSCLC).
- The efficacy of ICIs in NSCLC with specific EGFR mutations, such as exon 20 insertion mutations (ex20ins), is not well-established due to patient exclusion from clinical trials.
- EGFR ex20ins mutations are a distinct subset of EGFR-mutated NSCLC with unique clinical characteristics.
Purpose of the Study:
- To compare the real-world outcomes of ICI treatment in patients with EGFR ex20ins NSCLC versus wildtype NSCLC (wt-NSCLC).
- To evaluate the effectiveness of ICIs as a first-line therapy in these patient populations.
Main Methods:
- A retrospective, real-world study using the Flatiron Health database (2015-2020).
- Included patients with advanced NSCLC, comparing those with EGFR ex20ins to wt-NSCLC.
- Primary endpoint: real-world time to next therapy (rwTTNT). Secondary endpoint: real-world overall survival (rwOS).
Main Results:
- The study included 59 patients with EGFR ex20ins NSCLC and 5365 with wt-NSCLC.
- Patients with EGFR ex20ins had a 58% increased risk of shorter time to next therapy (rwTTNT) compared to wt-NSCLC (aHR 1.58; P=.0012).
- Median rwTTNT for first-line ICI was 3.7 months for EGFR ex20ins NSCLC versus 5.8 months for wt-NSCLC. No significant difference in rwOS was observed.
Conclusions:
- Immune checkpoint inhibitor therapy appears less effective in NSCLC patients with EGFR ex20ins mutations compared to wildtype NSCLC.
- Tumors with EGFR ex20ins mutations demonstrate reduced responsiveness to immune checkpoint inhibition.
- These findings align with previous research on other EGFR mutations, suggesting a broader pattern of resistance to ICIs in EGFR-mutated NSCLC.
