Treatment and survival of patients with EGFR -mutated non-small cell lung cancer and leptomeningeal metastasis: A retrospective cohort analysis

Kuiper, J.; Hendriks, Lizza; Wekken, Anthonie J. van der; Langen, Adrianus J. de; Bahce, Idris; Thunnissen, Erik; Heideman, Daniëlle A.M.; Berk, Yvonne; Buijs, Ed J.M.; Speel, Ernst‐Jan M.; Krouwels, Frans H.; Smit, Hans; Groen, Harry J.M.; Dingemans, Anne‐Marie C.; Smit, Egbert F.

doi:10.1016/j.lungcan.2015.05.023

Cited by 111 publications

(82 citation statements)

References 37 publications

(56 reference statements)

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“…For afatinib, the cerebral response rate was 35% and the cerebral disease control rate was 66% in patients with CNS disease [7]. There have been a few reports of patients with leptomeningeal carcinomatosis who were treated with EGFR-TKIs, and these have demonstrated that some of the patients achieved prolonged survival [7,8,9,10,11,12,13,14,15,16,17]. …”

Section: Discussionmentioning

confidence: 99%

Clinical Efficacy of Afatinib Treatment for a Patient with Leptomeningeal Carcinomatosis

Kawaguchi

Hanaoka²,

Hayashi³

et al. 2016

Chemotherapy

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Leptomeningeal metastases occur in 1% of patients with non-small-cell lung cancer. There have been several reports on the treatment of leptomeningeal metastases with afatinib. Our patient was a 41-year-old woman who had never smoked and was diagnosed with stage IV adenocarcinoma of the lung with an epidermal growth factor receptor (EGFR) mutation. She was treated with afatinib for the recurrence of leptomeningeal metastases. After the treatment with afatinib was initiated, the neurological symptoms dramatically regressed, and she achieved progression-free survival for 7 months. The concentration of afatinib in the cerebrospinal fluid (CSF) ranged from 0.05 to 0.14 ng/mL, and the penetration rate of afatinib from the plasma to the CSF ranged from 0.28 to 0.40%. This concentration might be sufficient to achieve a clinical effect for leptomeningeal carcinomatosis. Therefore, afatinib administered at the usual doses may be an effective treatment for leptomeningeal carcinomatosis of EGFR-mutated or EGFR-tyrosine kinase inhibitor-sensitive lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Clinical Efficacy of Afatinib Treatment for a Patient with Leptomeningeal Carcinomatosis

Kawaguchi

Hanaoka²,

Hayashi³

et al. 2016

Chemotherapy

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“…A response to therapy and a prolonged overall survival is observed especially in patients with breast cancer (median survival 7-12 months) [31,32], whereas patients with melanoma [33] or lung cancer (irrespective of EGFR mutation [34][35][36]) have a short median survival of approximately 4 months. Nevertheless, even for the latter an extended overall survival (> 12 months) with therapy is possible in individual cases.…”

Section: Prognosismentioning

confidence: 99%

Therapy of leptomeningeal metastasis in solid tumors

Mack

Baumert

Schäfer

et al. 2016

Cancer Treatment Reviews

136

100

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“…About 9% to 10% of patients with NSCLC with EGFRactivating mutations will develop LM either at initial diagnosis or during TKI treatment (9,10). LM is often associated with poor prognosis and represents a terminal event of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

“…LM is often associated with poor prognosis and represents a terminal event of NSCLC. The median overall survival (OS) after LM diagnosis is 3.1 to 11 months, with $60% death due to LM or LM together with systemic lesions (9)(10)(11)(12)(13). So far, there is no effective treatment, though preliminary clinical activities of osimertinib and AZD3759 in patients with NSCLC with LM have been reported (14,15), and other CNSpenetrant TKIs such as tesevatinib are being developed.…”

Section: Introductionmentioning

confidence: 99%

Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

Fan

Zhu²,

et al. 2018

Clinical Cancer Research

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Purpose: Leptomeningeal metastasis (LM) is a detrimental complication of non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the underlying mechanisms of the metastasis process are still poorly understood.Experimental Design: We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF), and matched normal controls from epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with LM.Results: The status of EGFR-activating mutations was highly concordant between primary tumor and CSF. PIK3CA aberrations were high in these patients, implicating an association with LM risk. Intriguingly, low overlapping of somatic protein-changing variants was observed between paired CSF and primary lesions, exhibiting tumor heterogeneity and genetic divergence. Moreover, genes with CSF-recurrent genomic alterations were predominantly involved in cell-cycle regulation and DNA-damage response (DDR), suggesting a role of the pathway in LM development.Conclusions: Our study has shed light on the genomic variations of NSCLC-LM, demonstrated genetic heterogeneity and divergence, uncovered involvement of cell-cycle and DDR pathway, and paved the way for potential therapeutic approaches to this unmet medical need.

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Treatment and survival of patients with EGFR -mutated non-small cell lung cancer and leptomeningeal metastasis: A retrospective cohort analysis

Cited by 111 publications

References 37 publications

Clinical Efficacy of Afatinib Treatment for a Patient with Leptomeningeal Carcinomatosis

Clinical Efficacy of Afatinib Treatment for a Patient with Leptomeningeal Carcinomatosis

Therapy of leptomeningeal metastasis in solid tumors

Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

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