A Nationwide Study on the Impact of Routine Testing for EGFR Mutations in Advanced NSCLC Reveals Distinct Survival Patterns Based on EGFR Mutation Subclasses

Abstract

EGFR mutation analysis in non-small-cell lung cancer (NSCLC) patients is currently standard-of-care. We determined the uptake of EGFR testing, test results and survival of EGFR-mutant NSCLC patients in the Netherlands, with the overall objective to characterize the landscape of clinically actionable EGFR mutations and determine the role and clinical relevance of uncommon and composite EGFR mutations. Non-squamous NSCLC patients diagnosed in 2013, 2015 and 2017 were identified in the Netherlands Cancer Registry (NCR) and matched to the Dutch Pathology Registry (PALGA). Overall, 10,254 patients were included. Between 2013–2017, the uptake of EGFR testing gradually increased from 72.7% to 80.9% (p < 0.001). Multi-gene testing via next-generation sequencing (increased from 7.8% to 78.7% (p < 0.001), but did not affect the number of detected EGFR mutations (n = 925; 11.7%; 95% confidence interval (CI), 11.0–12.4) nor the distribution of variants. For patients treated with first-line EGFR inhibitors (n = 651), exon 19 deletions were associated with longer OS than L858R (HR 1.58; 95% CI, 1.30–1.92; p < 0.001) or uncommon, actionable variants (HR 2.13; 95% CI, 1.60–2.84; p < 0.001). Interestingly, OS for patients with L858R was similar to those with uncommon, actionable variants (HR 1.31; 95% CI, 0.98–1.75; p = 0.069). Our analysis indicates that grouping exon 19 deletions and L858R into one class of ‘common’ EGFR mutations in a clinical trial may mask the true activity of an EGFR inhibitor towards specific mutations.

Impact of time-to-treatment on survival for advanced non-small cell lung cancer patients in the Netherlands: a nationwide observational cohort study

“…Molecular diagnostics have become standard in clinical routine to identify patients who may benefit from targeted therapy or immunotherapy 7. However, previous Dutch studies showed that the molecular testing rate increased significantly from 73% in 2013 to 81% in 2017 41 42. Though, about 15% of the patients did not receive targeted therapy despite presence of a targetable mutation 43.…”

A population-based study describing characteristics, survival and the effect of TKI treatment on patients with EGFR mutated stage IV NSCLC in the Netherlands

“…Furthermore, not starting TKI might be associated with molecular testing. Testing for EGFR mutations has been standard-of-care in the Netherlands since 2011, but next generation sequencing for EGFR has gradually been implemented into the routine setting for nonsquamous NSCLC [18]. Although, the Netherlands is a small western country with easy access to care, especially in the early years of study patients might have chosen for other first-line treatments due to limited availability of EGFR testing or treatment near their home.…”

A Real-World Systematic Analysis of Driver Mutations’ Prevalence in Early- and Advanced-Stage NSCLC: Implications for Targeted Therapies in the Adjuvant Setting

“…It is possible that the association of EGFR mutations with favorable prognostic factors might act as a confounding factor in these types of analysis. Furthermore, given the large spectrum of EGFR mutations in LUAD, it remains to be seen whether prognosis is affected differently by distinct mutations or mutation subgroups [ 30 ]. TP53 status was also informative: thus, in line with previous observations [ 31 ], our study found that TP53 mutations had negative prognostic value in early-stage LUAD patients.…”