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EGFR testing and erlotinib use in non-small cell lung cancer patients in Kentucky.

ABSTRACT: This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from 0.1% to 10.6% over the evaluated period while erlotinib use ranged from 3.4% to 5.4%. Factors associated with no EGFR testing were older age, male gender, enrollment in Medicaid or Medicare, smoking, and geographic region. Factors associated with not receiving erlotinib included older age, male gender, enrollment in Medicare or Medicaid, and living in moderate to high poverty. Survival analysis demonstrated EGFR testing or erlotinib use was associated with a higher likelihood of survival. EGFR testing and erlotinib prescribing were slow to be implemented in our predominantly rural state. While population-level factors likely contributed, patient factors, including geographic location (areas with high poverty rates and rural regions) and insurance type, were associated with lack of use, highlighting rural disparities in the implementation of cancer precision medicine.

SUBMITTER: Larson KL

PROVIDER: S-EPMC7433873 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Real-World Patterns of EGFR Testing and Treatment with Erlotinib for Non-Small Cell Lung Cancer in the United States.

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Efficacy of erlotinib as neoadjuvant regimen in EGFR-mutant locally advanced non-small cell lung cancer patients.

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Dose-Dependent Mutation Rates Determine Optimum Erlotinib Dosing Strategies for EGFR Mutant Non-Small Cell Lung Cancer Patients.

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Disparities and Trends in Genetic Testing and Erlotinib Treatment among Metastatic Non-Small Cell Lung Cancer Patients.

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| S-EPMC6500471 | biostudies-literature

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Project description: Not available

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Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer.

Project description:Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib are novel effective agents in the treatment of EGFR-driven lung cancer, but their clinical impact is often impaired by acquired drug resistance through the secondary T790M EGFR mutation. To overcome this problem, we analysed the metabonomic differences between two independent pairs of erlotinib-sensitive/resistant cells and discovered that glutathione (GSH) levels were significantly reduced in T790M EGFR cells. We also found that increasing GSH levels in erlotinib-resistant cells re-sensitised them, whereas reducing GSH levels in erlotinib-sensitive cells made them resistant. Decreased transcription of the GSH-synthesising enzymes (GCLC and GSS) due to the inhibition of NRF2 was responsible for low GSH levels in resistant cells that was directly linked to the T790M mutation. T790M EGFR clinical samples also showed decreased expression of these key enzymes; increasing intra-tumoural GSH levels with a small-molecule GST inhibitor re-sensitised resistant tumours to erlotinib in mice. Thus, we identified a new resistance pathway controlled by EGFR T790M and a therapeutic strategy to tackle this problem in the clinic.

| S-EPMC5037574 | biostudies-literature

EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer.

Project description:Activating epidermal growth factor receptor (EGFR) mutations are recognized biomarkers for patients with metastatic non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). EGFR TKIs can also have activity against NSCLC without EGFR mutations, requiring the identification of additional relevant biomarkers. Previous studies on tumor EGFR protein levels and EGFR gene copy number revealed inconsistent results. The aim of the study was to identify novel biomarkers of the response to TKIs in NSCLC by investigating whole genome expression at the exon-level. We used exon arrays and clinical samples from a previous trial (SAKK19/05) to investigate the expression variations at the exon-level of 3 genes potentially playing a key role in modulating treatment response: EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and vascular endothelial growth factor (VEGFA). We identified the expression of EGFR exon 18 as a new predictive marker for patients with untreated metastatic NSCLC treated with bevacizumab and erlotinib in the first line setting. The overexpression of EGFR exon 18 in tumor was significantly associated with tumor shrinkage, independently of EGFR mutation status. A similar significant association could be found in blood samples. In conclusion, exonic EGFR expression particularly in exon 18 was found to be a relevant predictive biomarker for response to bevacizumab and erlotinib. Based on these results, we propose a new model of EGFR testing in tumor and blood.

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RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small cell lung cancer: exposure-response relationship.

Project description:PurposeIn RELAY, ramucirumab plus erlotinib (RAM + ERL) improved progression-free survival (PFS) in patients with untreated, metastatic, EGFR-mutated, non-small cell lung cancer (NSCLC). Here, we present the exposure-response relationship of RAM from RELAY.MethodsPatients received ERL (150 mg/day) with either RAM (10 mg/kg) or placebo (PBO + ERL) every 2 weeks (Q2W). A population pharmacokinetic model predicted RAM minimum concentration after first dose (Cmin,1), and at steady state (Cmin,ss), which were used to evaluate correlation between RAM exposure and efficacy and safety. The Kaplan-Meier method and Cox regression analyses were utilized to evaluate exposure-efficacy by Cmin,1 quartile. Exposure-safety was evaluated by assessing incidence rates for safety parameters by Cmin,ss quartile, with ordered categorical analysis used for ALT/AST only.ResultsAnalyses included 216 patients treated with RAM + ERL and 225 patients treated with PBO + ERL. Adjusting for significant baseline covariates, no exposure-efficacy relationship was identified in RELAY: PFS hazard ratio (mean, 95% confidence intervals) for the Cmin,1 quartiles were 0.67 (0.45-0.99), 0.77 (0.53-1.12), 0.57 (0.38-0.84), and 0.50 (0.33-0.76). No apparent exposure-safety relationship was observed for selected safety endpoints, including Grade ≥ 3 hypertension, diarrhea, and dermatitis acneiform, and any grade hypertension, any grade and Grade ≥ 3 proteinuria, and any grade ALT/AST increased within liver failure/liver injury.ConclusionsNo association was observed between RAM exposure and response, suggesting that the RELAY regimen of RAM 10 mg/kg Q2W with ERL is an optimized, efficacious, and safe first-line treatment for patients with untreated, metastatic, EGFR-mutated NSCLC.Trial registrationClinicalTrials.gov, NCT02411448.

| S-EPMC9360106 | biostudies-literature

Targeted treatment of mutated EGFR-expressing non-small-cell lung cancer: focus on erlotinib with companion diagnostics.

Project description:Deeper understanding of the pathobiology of non-small-cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in the progression to metastatic disease. The discovery of epidermal growth factor receptor (EGFR) mutations in 15%-20% of lung adenocarcinomas and the associated response to EGFR tyrosine kinase inhibitors have provided a successful avenue of attack in late-stage adenocarcinomas. Use of the EGFR tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib is limited to patients who have adenocarcinomas with known activating EGFR mutations. However, the EGFR mutation testing landscape is varied and includes many screening and targeted methods, each with its own benefits and limitations. These tests can simplify the drug discovery process, make clinical trials more efficient and informative, and individualize cancer therapy. In practice, the choice of method should be determined by the nature of the sample to be tested, the testing laboratory's expertise and access to equipment, and whether the detection of only known activating EGFR mutations, or of all possible mutations, is required. Development of companion diagnostic tests for this identification is advancing; nevertheless, the use of such tests merits greater attention.

| S-EPMC5217512 | biostudies-literature

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