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Tumor evolution in epidermal growth factor receptor mutated non-small cell lung cancer.

ABSTRACT: As the incidence of cancer increases worldwide there is an unmet need to understand cancer evolution to improve patient outcomes. Our growing knowledge of cancer cells' clonal expansion, heterogeneity, adaptation, and relationships within the tumor immune compartment and with the tumor microenvironment has made clear that cancer is a disease that benefits from heterogeneity and evolution. This review outlines recent knowledge of non-small cell lung cancer (NSCLC) pathogenesis and tumor progression from an evolutionary standpoint, focused on the role of oncogenic driver mutations as epidermal growth factor receptor (EGFR). Understanding lung cancer evolution during tumor development, growth, and under treatment pressures is crucial to improve therapeutic interventions and patient outcomes.

SUBMITTER: Velazquez AI

PROVIDER: S-EPMC7330358 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Tumor evolution in epidermal growth factor receptor mutated non-small cell lung cancer.

Velazquez Ana I AI McCoach Caroline E CE

Journal of thoracic disease 20200501 5

As the incidence of cancer increases worldwide there is an unmet need to understand cancer evolution to improve patient outcomes. Our growing knowledge of cancer cells' clonal expansion, heterogeneity, adaptation, and relationships within the tumor immune compartment and with the tumor microenvironment has made clear that cancer is a disease that benefits from heterogeneity and evolution. This review outlines recent knowledge of non-small cell lung cancer (NSCLC) pathogenesis and tumor progressi ...[more]

PMID: 32642202

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Project description:ObjectiveTo review and summarize the characteristics of the tumor immune microenvironment (TIME) in EGFR-mutated non-small cell lung cancer (NSCLC) after EGFR-TKI treatment and its role in TKI resistance.BackgroundLung cancer is one of the most commonly diagnosed cancer and the leading cause of death from cancer in both men and women around the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are considered a first-line treatment for EGFR-mutated NSCLC. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, with a median progression-free survival (PFS) of 9-14 months. As immunotherapy has developed, it has become apparent that interactions between the TIME and tumor cells also affect EGFR-TKI treatment. The TIME comprises a variety of components but previous studies of the TIME following EGFR-TKI therapy of NSCLC are inconsistent. Here, we reviewed the characteristics of the TIME in NSCLC after EGFR-TKI treatment and its role in TKI resistance.MethodsPubMed, Embase, and Web of Science were searched to July 1, 2021 with the following key words: "NSCLC", "EGFR", and "immunotherapy".ConclusionsThe TIME of EGFR-mutated NSCLC is different from that of non-mutated NSCLC, an explanation for EGFR-mutated NSCLC displaying a poor response to ICIs. The TIME of EGFR-mutated NSCLC also changes during treatment with EGFR-TKIs. The TIME in EGFR-TKI-resistant lung cancer can be summarized as follows: (I) compared with EGFR-TKI-sensitive tumors, EGFR-TKI-resistant tumors have a greater number of immunosuppressive cells and fewer immune-activated cells, while the tumor microenvironment is in an immunosuppressive state; (II) tumor cells and immunosuppressive cells secrete multiple negative immune regulatory factors, inhibit the recognition and presentation of tumor antigens and the antitumor effect of immune cells, resulting in immune escape; 3.EGFR-TKI-resistant tumors promote EMT. These three characteristics interact, resulting in a regulatory signaling network, which together leads to EGFR-TKI resistance.

Project description:Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is clinically effective in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, the use of this treatment is limited by its high cost. A cost-effectiveness analysis of different sequences of osimertinib administration in China and the United States was conducted in the present study. Markov models were established based on data from the FLAURA and AURA3 trials. First-line osimertinib was compared with both first-generation EGFR-TKIs and second-line osimertinib after the failure of first-generation EGFR-TKIs. The analysis also considered different payment modalities available in China. Additionally, one-way and probability sensitivity analyses, with a willingness-to-pay threshold (WTP) of three times the per capita gross domestic product [$27,783/quality-adjusted life year (QALY) for China and $100,000/QALY for the United States], were performed. The first-line osimertinib group displayed higher QALYs and costs than those of the first-generation EGFR-TKI group. The first generation EGFR-TKI group displayed an incremental cost-effectiveness ratio (ICER) of $212,252/QALY in China and $151,922/QALY in the United States. In addition, the ICERs were negative in the second-line osimertinib group, with higher QALYs and lower costs compared with those in the first-line osimertinib group. Furthermore, osimertinib company donation was of benefit in China, with an average cost-effectiveness of $836/QALY. The one-way sensitivity analysis highlighted the influence of utilities in different states. First-line osimertinib could be cost-effective either with higher WTP or a price reduction of 68% in China and 9% in the United States. Although first-line osimertinib therapy could have health benefits, it was not cost-effective compared with first-line first-generation EGFR-TKIs and second-line osimertinib therapy. However, paying via company donation may be a good choice in China.

Dataset Information

Tumor evolution in epidermal growth factor receptor mutated non-small cell lung cancer.

Publications

Tumor evolution in epidermal growth factor receptor mutated non-small cell lung cancer.

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