Incomplete uptake of EGFR mutation testing and its impact on estimation of mutation prevalence in patients with non-squamous NSCLC: A population-based study in New Zealand

Tin, Sandar Tin; McKeage, Mark J.; Khwaounjoo, Prashannata; Thi, Aye Myat; Elwood, J. Mark

doi:10.1016/j.canep.2018.09.004

Cited by 11 publications

(17 citation statements)

References 14 publications

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“…Our earlier work showed that EGFR mutation testing increased from 3.7% of all patients in 2010 to 64.6% in 2014 in this population-based retrospective cohort [20]. In parallel, recorded EGFR mutation rates decreased from 43.8% in 2010 to 16.8% in 2014, reflecting decreases in selective testing [22]. Taking into account this variation, we assessed the external validity of the model in the independent earlier period dataset, and the results were similar to those in the development group.…”

Section: Discussionmentioning

confidence: 58%

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Development and validation of a predictive model for estimating EGFR mutation probabilities in patients with non-squamous non-small cell lung cancer in New Zealand

et al. 2020

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Background: Targeted treatment with Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) is superior to systemic chemotherapy in non-small cell lung cancer (NSCLC) patients with EGFR gene mutations. Detection of EGFR mutations is a challenge in many patients due to the lack of suitable tumour specimens for molecular testing or for other reasons. EGFR mutations are more common in female, Asian and never smoking NSCLC patients. Methods: Patients were from a population-based retrospective cohort of 3556 patients diagnosed with non-squamous non-small cell lung cancer in northern New Zealand between 1 Feb 2010 and 31 July 2017. A total of 1694 patients were tested for EGFR mutations, of which information on 1665 patients was available for model development and validation. A multivariable logistic regression model was developed based on 1176 tested patients, and validated in 489 tested patients. Among 1862 patients not tested for EGFR mutations, 129 patients were treated with EGFR-TKIs. Their EGFR mutation probabilities were calculated using the model, and their duration of benefit and overall survival from the start of EGFR-TKI were compared among the three predicted probability groups: < 0.2, 0.2-0.6, and > 0.6. Results: The model has three predictors: sex, ethnicity and smoking status, and is presented as a nomogram to calculate EGFR mutation probabilities. The model performed well in the validation group (AUC = 0.75). The probability cut-point of 0.2 corresponds 68% sensitivity and 78% specificity. The model predictions were related to outcome in a group of TKItreated patients with no biopsy testing available (n = 129); in subgroups with predicted probabilities of < 0.2, 0.2-0.6, and > 0.6, median overall survival times from starting EGFR-TKI were 4.0, 5.5 and 18.3 months (p = 0.02); and median times remaining on EGFR-TKI treatment were 2.0, 4.2, and 14.0 months, respectively (p < 0.001). Conclusion: Our model may assist clinical decision making for patients in whom tissue-based mutation testing is difficult or as a supplement to mutation testing.

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Section: Discussionmentioning

confidence: 58%

“…Māori and Pacific people have a higher incidence of lung cancer and poorer survival, compared to the New Zealand European population [49]. But, the testing rate was particularly low in Māori patients compared to other ethnic groups [22]. Our model may be helpful in addressing ethnic disparity in lung cancer patients in New Zealand.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a predictive model for estimating EGFR mutation probabilities in patients with non-squamous non-small cell lung cancer in New Zealand

et al. 2020

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“…EGFR mutation has been proven to be more common in female, Asian, non-smoker and adenocarcinoma lung cancer patients internationally 37−39 . In New Zealand, our previous study showed that EGFR mutation was more prevalent in female, in Asian and Paci ca compared to New Zealand European, and in non-smokers compared to current smokers 33,36 . Considering statistical signi cance of the factors and interactions between factors may be necessary for developing survival predictive models in the future.…”

Section: Discussionmentioning

confidence: 95%

“…Although our cohort included a considerably large number of patients (n = 1534), the EGFR mutation was positive in 20% of patients (n = 310), which limits the power of subgroup analyses. The EGFR mutation information was based on the patient population tested for EGFR mutation where testing was incomplete -the testing rate was 65% among eligible non-squamous NSCLC based on the same region data in 2014, and attributable to patient selection bias 36 . We plan to assess the changes when testing becomes more complete in the future.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with overall survival in patients with non-squamous NSCLC in New Zealand: A comparative analysis by EGFR gene mutation status

Aye

McKeage

Tin

et al. 2020

Preprint

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Introduction: Non-small cell lung cancer (NSCLC) is increasingly regarded as a heterogeneous group of diseases defined by specific gene mutations. Previous studies reported inconsistent results regarding the influence of epidermal growth factor receptor (EGFR) mutations on overall survival. This study assesses the effect of EGFR mutation on overall survival, and how the effects of other survival predictors are modified by EGFR mutation status, in non-squamous NSCLC patients.Methods: The study was based on a population-based cohort of 1534 non-squamous NSCLC patients who were registered in northern New Zealand between 1 February 2010 and 31 July 2017. Kaplan-Meier analyses and log-rank tests were performed to assess the overall survival among different patient groups. Cox regression survival analyses were used to explore the associations between clinico-pathological factors and overall survival in terms of EGFR mutation status. The factors included were age at diagnosis, sex, ethnicity, smoking status, performance status, metastasis status and site of tumour. Results: In this cohort, 20.2% had an EGFR mutation. The median overall survival was 0.79 years and 2.81 years in EGFR mutation-negative and mutation-positive groups respectively (log-rank p<0.0001). Metastasis status showed large and significant effects on overall survival in both EGFR mutation-negative and mutation-positive groups (hazard ratio, HR=3.6 and 3.3, respectively). In subgroup analyses by mutation status and metastasis status, overall survival decreased with an increase in age and decrease in performance status, and was lower in current smokers in all subgroups. In specific groups, females had lower survival only if mutation-positive; Māori had lower survival compared to NZ Europeans only if the disease was metastatic; and tumour site had significant effects on overall survival only in patients without metastasis. Conclusion: EGFR mutation status and metastasis are the main predictors for overall survival in non-squamous NSCLC patients in northern New Zealand. The effects of age, smoking status and performance status are similar in all subgroups, but the effects of sex, ethnicity and site of tumour vary depending on EGFR mutation and metastasis status.

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“…The study was approved by the Northern Health and Disability Ethics committee (No: 13/NTB/165/AM02) and registered (ACTRN12615000998549). More details about the study design and setting are described elsewhere …”

Section: Methodsmentioning

confidence: 99%

Screening for anaplastic lymphoma kinase (ALK) gene rearrangements in non‐small‐cell lung cancer in New Zealand

McKeage

Tin

Khwaounjoo

et al. 2020

Internal Medicine Journal

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Background Lung cancer is a major cause of death in New Zealand. In recent years, targeted therapies have improved outcomes. Aim To determine the uptake of anaplastic lymphoma kinase (ALK) testing, and the prevalence, demographic profile and outcomes of ALK‐positive non‐small‐cell lung cancer (NSCLC), in New Zealand, where no national ALK‐testing guidelines or subsidised ALK tyrosine kinase inhibitor (TKI) therapies are available. Methods A population‐based observational study reviewed databases to identify patients presenting with non‐squamous NSCLC over 6.5 years in northern New Zealand. We report the proportion tested for ALK gene rearrangements and the results. NSCLC samples tested by fluorescence in situ hybridisation were retested by next generation sequencing and ALK immunohistochemistry. A survival analysis compared ALK‐positive patients treated or not treated with ALK TKI therapy. Results From a total of 3130 patients diagnosed with non‐squamous NSCLC, 407 (13%) were tested for ALK gene rearrangements, and patient selection was variable and inequitable. Among those tested, 34 (8.4%) had ALK‐positive NSCLC. ALK‐positive disease was more prevalent in younger versus older patients, non‐smokers versus smokers and in Māori, Pacific or Asian ethnic groups than in New Zealand Europeans. Fluorescence in situ hybridisation, ALK immunohistochemistry and next generation sequencing showed broad concordance for detecting ALK–positive disease under local testing conditions. Among patients with ALK‐positive metastatic NSCLC, those treated with ALK TKI survived markedly longer than those not treated with ALK TKI (median overall survival 5.12 vs 0.55 years). Conclusion Lung cancer outcomes in New Zealand may be improved by providing national guidelines and funding policy for ALK testing and access to subsidised ALK TKI therapy.

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Incomplete uptake of EGFR mutation testing and its impact on estimation of mutation prevalence in patients with non-squamous NSCLC: A population-based study in New Zealand

Cited by 11 publications

References 14 publications

Development and validation of a predictive model for estimating EGFR mutation probabilities in patients with non-squamous non-small cell lung cancer in New Zealand

Development and validation of a predictive model for estimating EGFR mutation probabilities in patients with non-squamous non-small cell lung cancer in New Zealand

Factors associated with overall survival in patients with non-squamous NSCLC in New Zealand: A comparative analysis by EGFR gene mutation status

Screening for anaplastic lymphoma kinase (ALK) gene rearrangements in non‐small‐cell lung cancer in New Zealand

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