Factors associated with overall survival in a population-based cohort of non- squamous NSCLC patients from northern New Zealand: A comparative analysis by EGFR mutation status

Aye, Phyu Sin; McKeage, Mark J.; Tin, Sandar Tin; Khwaounjoo, Prashannata; Elwood, J. Mark

doi:10.1016/j.canep.2020.101847

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…Previous reports on nationwide real-world data regarding the effect of EGFR mutation status and response to EGFR inhibitors generally lack detailed information with respect to EGFR mutation type [ 26 , 31 , 46 , 47 , 48 ]. In smaller cohorts, EGFR mutation status and response rates have been reported, but irrespective of evidence of response to first- and second-generation EGFR-TKI, often including T790M resistance mutations, exon 20 insertions and variants of unknown significance [ 49 , 50 , 51 , 52 , 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

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

Koopman

Garcia

Kuijpers³

et al. 2021

Cancers

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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.

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Section: Discussionmentioning

confidence: 99%

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

Koopman

Garcia

Kuijpers³

et al. 2021

Cancers

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“…The research project described in this protocol will provide important new information about the everyday impacts, both beneficial and harmful, arising from the introduction of erlotinib and gefitinib into routine clinical use for treating advanced EGFR mutation–positive lung cancer in NZ a little more than 1 decade ago. Previous studies in this area have been limited to evaluations of the impact and uptake of the introduction of EGFR mutation testing in the northern region of NZ [ 4 , 30 - 32 ]. Currently, few data exist on the effectiveness and safety of erlotinib and gefitinib in the general NZ patient population and on the contributions made by concomitant medications and other factors to adverse outcomes in this setting of routine care.…”

Section: Discussionmentioning

confidence: 99%

Erlotinib or Gefitinib for Treating Advanced Epidermal Growth Factor Receptor Mutation–Positive Lung Cancer in Aotearoa New Zealand: Protocol for a National Whole-of-Patient-Population Retrospective Cohort Study and Results of a Validation Substudy

Aye,

Barnes,

Laking

et al. 2024

JMIR Res Protoc

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Background Starting in 2010, the epidermal growth factor receptor (EGFR) kinase inhibitors erlotinib and gefitinib were introduced into routine use in Aotearoa New Zealand (NZ) for treating advanced lung cancer, but their impact in this setting is unknown. Objective The study described in this protocol aims to understand the effectiveness and safety of these new personalized lung cancer treatments and the contributions made by concomitant medicines and other factors to adverse outcomes in the general NZ patient population. A substudy aimed to validate national electronic health databases as the data source and the methods for determining patient eligibility and identifying outcomes and variables. Methods This study will include all NZ patients with advanced EGFR mutation–positive lung cancer who were first dispensed erlotinib or gefitinib before October 1, 2020, and followed until death or for at least 1 year. Routinely collected health administrative and clinical data will be collated from national electronic cancer registration, hospital discharge, mortality registration, and pharmaceutical dispensing databases by deterministic data linkage using National Health Index numbers. The primary effectiveness and safety outcomes will be time to treatment discontinuation and serious adverse events, respectively. The primary variable will be high-risk concomitant medicines use with erlotinib or gefitinib. For the validation substudy (n=100), data from clinical records were compared to those from national electronic health databases and analyzed by agreement analysis for categorical data and by paired 2-tailed t tests for numerical data. Results In the validation substudy, national electronic health databases and clinical records agreed in determining patient eligibility and for identifying serious adverse events, high-risk concomitant medicines use, and other categorical data with overall agreement and κ statistic of >90% and >0.8000, respectively; for example, for the determination of patient eligibility, the comparison of proxy and standard eligibility criteria applied to national electronic health databases and clinical records, respectively, showed overall agreement and κ statistic of 96% and 0.8936, respectively. Dates for estimating time to treatment discontinuation and other numerical variables and outcomes showed small differences, mostly with nonsignificant P values and 95% CIs overlapping with zero difference; for example, for the dates of the first dispensing of erlotinib or gefitinib, national electronic health databases and clinical records differed on average by approximately 4 days with a nonsignificant P value of .33 and 95% CIs overlapping with zero difference. As of May 2024, the main study is ongoing. Conclusions A protocol is presented for a national whole-of-patient-population retrospective cohort study designed to describe the safety and effectiveness of erlotinib and gefitinib during their first decade of routine use in NZ for treating EGFR mutation–positive lung cancer. The validation substudy demonstrated the feasibility and validity of using national electronic health databases and the methods for determining patient eligibility and identifying the study outcomes and variables proposed in the study protocol. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12615000998549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368928 International Registered Report Identifier (IRRID) DERR1-10.2196/51381

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Driver and novel genes correlated with metastasis of non-small cell lung cancer: A comprehensive analysis

Ni²,

Yang

et al. 2021

Pathology - Research and Practice

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Factors associated with overall survival in a population-based cohort of non- squamous NSCLC patients from northern New Zealand: A comparative analysis by EGFR mutation status

Cited by 4 publications

References 30 publications

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

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

Erlotinib or Gefitinib for Treating Advanced Epidermal Growth Factor Receptor Mutation–Positive Lung Cancer in Aotearoa New Zealand: Protocol for a National Whole-of-Patient-Population Retrospective Cohort Study and Results of a Validation Substudy

Driver and novel genes correlated with metastasis of non-small cell lung cancer: A comprehensive analysis

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