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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.

SUBMITTER: Koopman B

PROVIDER: S-EPMC8307492 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard-of-care first-line (1L) treatment for EGFR mutation-positive advanced/metastatic non-small cell lung cancer. In 2015, osimertinib, a third-generation EGFR-TKI, received US accelerated approval for second-line (2L) EGFR T790M-positive non-small cell lung cancer treatment. The objective of this US study was to characterize treatment patterns, attrition, and survival in EGFR mutation-positive non-small cell lung cancer, after 1L first-/second-generation EGFR-TKI treatment.MethodsWe retrospectively analyzed 1029 patients diagnosed with stage IIIB/IV non-small cell lung cancer from 1 January, 2011 to 31 December, 2018 using the US electronic medical record CancerLinQ Discovery® database. Demographic/disease characteristics, EGFR mutations, treatments, and death dates were collected.ResultsFrom 1 January, 2011 to 31 December, 2014 (< 2015 cohort), 519 patients received 1L EGFR-TKIs and 510 between 1 January, 2015 and 31 December, 2018 (≥ 2015 cohort). Median follow-up from advanced diagnosis was 19.8 months (interquartile range: 9.9-33.4 months). Twenty-eight percent of patients (288/1029) died without receiving 2L, and 52% (539/1029) initiated 2L with 35% (186/539) receiving osimertinib; in the < 2015 and ≥ 2015 cohorts, the same proportion initiated 2L (52%; 272/519 vs 267/510, respectively). Median overall survival from advanced diagnosis for patients initially diagnosed with stage I-IIIA disease was 43.3 months (95% confidence interval 30.9-73.7), vs 26.4 months (95% confidence interval 24.4-28.1) for stage IIIB-IV; all-cause mortality hazard ratio: 1.56 (95% confidence interval 1.2-2.0; p = 0.001).ConclusionsWe identified disease stage, performance status, and central nervous system metastasis as survival predictors, highlighting the importance of optimal 1L treatment selection. Over a quarter of patients died before initiating 2L; half progressed after 1L and received 2L, of whom a third received 2L osimertinib.

Project description:To assess the role of radiomic features in distinguishing squamous and adenocarcinoma subtypes of nonsmall cell lung cancers (NSCLC) and predict EGFR mutations.Institution Review Board-approved study included chest CT scans of 93 consecutive patients (43 men, 50 women, mean age 60 ± 11 years) with biopsy-proven squamous and adenocarcinoma lung cancers greater than 1 cm. All cancers were evaluated for epidermal growth factor receptor (EGFR) mutation. The clinical parameters such as age, sex, and smoking history and standard morphology-based CT imaging features such as target lesion longest diameter (LD), longest perpendicular diameter (LPD), density, and presence of cavity were recorded. The radiomics data was obtained using commercial CT texture analysis (CTTA) software. The CTTA was performed on a single image of the dominant lung lesion. The predictive value of clinical history, standard imaging features, and radiomics was assessed with multivariable logistic regression and receiver operating characteristic (ROC) analyses.Between adenocarcinoma and squamous cell carcinomas, ROC analysis showed significant difference in 3/11 radiomic features (entropy, normalized SD, total) [AUC 0.686-0.744, P = .006 to <.0001], 1/3 clinical features (smoking) [AUC 0.732, P = .001], and 2/3 imaging features (LD and LPD) [AUC 0.646-0658, P = .020 to .032]. ROC analysis for probability variables showed higher values for radiomics (AUC 0.800, P < .0001) than clinical (AUC 0.676, P = .017) and standard imaging (AUC 0.708, P < .0001). Between EGFR mutant and wild-type adenocarcinoma, ROC analysis showed significant difference in 2/11 radiomic features (kurtosis, K2) [AUC 0.656-0.713, P = .03 to .003], 1/3 clinical features (smoking) [AUC 0.758, P < .0001]. The combined probability variable for radiomics, clinical and imaging features was higher (AUC 0.890, P < .0001) than independent probability variables.The radiomics evaluation adds incremental value to clinical history and standard imaging features in predicting histology and EGFR mutations.

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

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