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Central nervous system metastases and oligoprogression during treatment with tyrosine kinase inhibitors in oncogene-addicted non-small cell lung cancer: how to treat and when?

ABSTRACT: Up to 70% of non-small cell lung cancer (NSCLC) patients develop central nervous system (CNS) metastases during the course of their disease, especially those with oncogenic drivers treated with a first-generation tyrosine kinase inhibitor (TKI), because of the relatively poor CNS penetration. CNS metastases are associated with a negative impact on quality of life and survival. As, with the introduction of newer generation TKIs, the survival rates are increasing in this particular population, treatment and/or prevention of CNS metastases becomes even more relevant and the TKI with the best CNS efficacy should be selected. Unfortunately, CNS efficacy data in clinical trials are not fully comparable. Furthermore, oligoprogression to the brain without extracranial progression regularly occurs in the oncogenic driver population and both local therapy and switch of systemic therapy are possible treatment options. However, the best order of systemic and local therapy is still not precisely known. In this narrative review, we will summarize incidence and treatment of CNS metastases in oncogene driven NSCLC, including the optimal treatment of CNS oligometastatic disease (synchronous as well as oligoprogressive).

SUBMITTER: Schoenmaekers JJAO

PROVIDER: S-EPMC7815343 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Central nervous system metastases and oligoprogression during treatment with tyrosine kinase inhibitors in oncogene-addicted non-small cell lung cancer: how to treat and when?

Schoenmaekers Janna Josephus Anna Oda JJAO Paats Marthe Sentijna MS Dingemans Anne-Marie Clasina AC Hendriks Lizza Elisabeth Lucia LEL

Translational lung cancer research 20201201 6

Up to 70% of non-small cell lung cancer (NSCLC) patients develop central nervous system (CNS) metastases during the course of their disease, especially those with oncogenic drivers treated with a first-generation tyrosine kinase inhibitor (TKI), because of the relatively poor CNS penetration. CNS metastases are associated with a negative impact on quality of life and survival. As, with the introduction of newer generation TKIs, the survival rates are increasing in this particular population, tre ...[more]

PMID: 33489821

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Project description:BackgroundLack of biomarkers and in vitro models has contributed to inadequate understanding of the mechanisms underlying the inferior clinical response to immune checkpoint inhibitors (ICIs) in patients with oncogene-driven non-small cell lung cancer (NSCLC).MethodsThe effect of small molecule tyrosine kinase inhibitors (TKIs) on peripheral blood mononuclear cells (PBMCs) in 34 patients with oncogene-driven NSCLC (cohort A) was compared with those from 35 NSCLC patients without oncogene-driven mutations received ICI (cohort B) or from 22 treatment-naïve NSCLC patients (cohort C). Data for each blood biomarker were summarized by mean and standard deviation and compared by Wilcoxon rank sum tests or Kruskal-Wallis tests with significance at 2-sided p value < 0.05. Co-culture of PBMCs and pleural effusion-derived tumor cells from individual patients with oncogene-driven NSCLC was used to determine the in vitro cytotoxicity of TKI and ICI.ResultsExcept for low CD3% in cohort A, there were no significant differences in other 12 blood biomarkers among the 3 cohorts at baseline. TKI treatment in cohort A was associated with significant increase in CD3% and decrease in total and absolute neutrophils (p < 0.05). In cohort B, patients with good clinical response to ICI treatment (N = 18) had significant increases in absolute lymphocyte counts (ALCs), CD4 and/or CD8 cell counts. Conversely, those patients with poor clinical response to ICI (N = 17) had significant decreases in these cell counts. Of the 27 patients with pre- and post-treatment blood samples in cohort A, 11 had poor clinical response to TKIs and decreased lymphocyte counts. Of the remaining 16 patients who had good clinical response to TKI therapy, 10 (62.5%) patients had decreased, and 6 (37.5%) patients had increased lymphocyte counts. Multicolor immunophenotyping of PBMCs revealed ICI treatment activated additional immune cell types that need further validation. We confirmed that TKI treatment could either antagonize or enhance the effect of ICIs in the co-culture assay using patient's tumor cells and PBMCs.ConclusionsTo the best of our knowledge, this is the first study showing that TKIs can have various effects on blood immune cells, which may affect their response to ICIs. Further validation of the blood biomarker and in vitro assay is warranted.

Dataset Information

Central nervous system metastases and oligoprogression during treatment with tyrosine kinase inhibitors in oncogene-addicted non-small cell lung cancer: how to treat and when?

Publications

Central nervous system metastases and oligoprogression during treatment with tyrosine kinase inhibitors in oncogene-addicted non-small cell lung cancer: how to treat and when?

Similar Datasets

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