A Nationwide Study on the Impact of Routine Testing for EGFR Mutations in Advanced NSCLC Reveals Distinct Survival Patterns Based on EGFR Mutation Subclasses.
Bart KoopmanBetzabel N Cajiao GarciaChantal C H J KuijpersRonald A M DamhuisAnthonie J van der WekkenHarry J M GroenEd M D SchuuringStefan M WillemsLéon C L T van KempenPublished in: Cancers (2021)
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.
Keyphrases
- small cell lung cancer
- epidermal growth factor receptor
- tyrosine kinase
- end stage renal disease
- clinical trial
- advanced non small cell lung cancer
- newly diagnosed
- ejection fraction
- prognostic factors
- copy number
- healthcare
- gene expression
- brain metastases
- randomized controlled trial
- young adults
- squamous cell carcinoma
- obstructive sleep apnea
- low grade
- genome wide
- clinical practice
- lymph node metastasis
- transcription factor
- open label
- pain management
- papillary thyroid