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[Management of Drug Therapy for Leptomeningeal Metastasis of Sensitive Driver Gene Positive Non-small Cell Lung Cancer].

ABSTRACT: Leptomeningeal metastasis (LM) is one of the serious complications of advanced non-small cell lung cancer (NSCLC), although the incidence is not high, the clinical symptoms are severe and the prognosis is poor. LM is prone to occur in patients with positive driver gene than negative. At present, the treatment of LM mainly includes molecular targeted therapy, systemic chemotherapy, whole brain radiotherapy, intrathecal chemotherapy and immunotherapy. Although there are many treatments, the efficacy of LM is still unsatisfactory. This article reviews the drug therapy of sensitive driver gene positive NSCLC LM.

SUBMITTER: Lu Z

PROVIDER: S-EPMC7467993 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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[Management of Drug Therapy for Leptomeningeal Metastasis of Sensitive Driver Gene Positive Non-small Cell Lung Cancer].

Lu Zhiqin Z Cai Jing J Zeng Zhimin Z Liu Anwen A

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20200806 8

Leptomeningeal metastasis (LM) is one of the serious complications of advanced non-small cell lung cancer (NSCLC), although the incidence is not high, the clinical symptoms are severe and the prognosis is poor. LM is prone to occur in patients with positive driver gene than negative. At present, the treatment of LM mainly includes molecular targeted therapy, systemic chemotherapy, whole brain radiotherapy, intrathecal chemotherapy and immunotherapy. Although there are many treatments, the effica ...[more]

PMID: 32758347

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Project description:BackgroundLeptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. There is currently no standard treatment for LM, and the efficacy of traditional intravenous drug treatment is low, making refractory LM a difficult problem. In this study, we evaluated the efficacy and safety of intrathecal chemotherapy (IC)-based regimens in patients with refractory LM.MethodsWe retrospectively enrolled NSCLC patients with confirmed LM who received IC and systemic therapy at the Second Affiliated Hospital of Nanchang University from December 2017 to July 2022. We analysed overall survival (OS), intracranial progression-free survival (iPFS), clinical response, and safety in these patients.ResultsA total of 41 patients were enrolled. The median number of IC treatments was seven (range: 2-22). Seven patients received intrathecal methotrexate, and 34 patients received intrathecal pemetrexed. Clinical manifestations related to LM improved after IC and systemic therapy in 28 (68.3%) patients. The median iPFS in the whole cohort was 8 months (95% confidence interval [CI]: 6.4-9.7 months), and the median OS was 10.1 months (95% CI: 6.8-13.4 months). Multivariate analysis of the 41 patients with LM using a Cox proportional risk model showed that bevacizumab was an independent prognostic factor in patients treated with combination therapy (p = 0.002; hazard ratio [HR] 0.240; 95% CI: 0.097-0.595). Poor ECOG performance status remained a significant predictor of poor prognosis for survival (p = 0.048; HR 2.560; 95% CI: 1.010-6.484). Myelosuppression was the major adverse event over all IC dose levels. There were 18 cases of myelosuppression, 15 cases of leukopenia, and nine cases of thrombocytopenia. Eleven patients had myelosuppression above grade 3, including four with thrombocytopenia and seven with leukopenia.ConclusionsCombination therapy based on IC had good curative effects, was safe to use, and was associated with prolonged survival in NSCLC patients with LM. The use of bevacizumab is a good prognostic factor for NSCLC LM patients with combination therapy.

Project description:BackgroundEGFR-mutant non-small cell lung cancer (NSCLC) is prone to leptomeningeal metastasis (LM) after Tyrosine kinase inhibitors (TKIs) treatment. Our previous study suggested that osimertinib plus bevacizumab was safe and effective in LM from EGFR-mutant NSCLC. This study aimed to compare the efficacy of osimertinib plus bevacizumab with osimertinib in EGFR-mutant NSCLC patients with LM.MethodsWe retrospectively reviewed the data from 27 LM patients with EGFR-mutant NSCLC who received osimertinib with or without bevacizumab at the Second Affiliated Hospital of Nanchang University. Next, we investigated the antitumor efficacy of osimertinib plus bevacizumab in an LM xenograft model using the H1975 (EGFR exon20 T790M and exon21 L858R) cell line. We examined the ability of osimertinib plus bevacizumab compared with osimertinib to penetrate the blood-brain barrier (BBB) and explored the potential mechanism.ResultsOur retrospective study observed the improved survival of LM patients in osimertinib plus bevacizumab group. The median overall survival (OS) of the patients who received osimertinib and bevacizumab (n = 16) compared with osimertinib group (n = 11) was 18.0 months versus 13.7 months (log-rank test, p = 0.046, HR = 2.867, 95% CI 1.007-8.162). The median intracranial Progression-free Survival (iPFS) was 10.6 months versus 5.5 months (log-rank test, p = 0.037, HR = 3.401, 95% CI 1.079-10.720). In the LM xenograft model with H1975 cells, the combined treatment significantly increased the effective intracranial concentration of osimertinib, modulated the level of E-cadherin and downregulated the levels of EGFR and downstream signaling pathways including p-AKT and reduced tumor microvessel density (TMD), indicated that combined osimertinib with bevacizumab may exhibit a synergistic effect in EGFR-mutant LM model possibly by modulating the level of E-cadherin.ConclusionsOur findings indicate the potential benefit of osimertinib plus bevacizumab in LM with EGFR-mutant NSCLC, and more larger sample size research are still needed.

Dataset Information

[Management of Drug Therapy for Leptomeningeal Metastasis of Sensitive Driver Gene Positive Non-small Cell Lung Cancer].

Publications

[Management of Drug Therapy for Leptomeningeal Metastasis of Sensitive Driver Gene Positive Non-small Cell Lung Cancer].

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