Rapid Response to the Combination of Lenvatinib and Pembrolizumab in Patients with Advanced Carcinomas (Lung Adenocarcinoma and Malignant Pleural Mesothelioma).
Rapid Response to the Combination of Lenvatinib and Pembrolizumab in Patients with Advanced Carcinomas (Lung Adenocarcinoma and Malignant Pleural Mesothelioma).
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DOI：
10.3390/cancers13143630
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发表时间：
2021-07-20
期刊：
影响因子：
5.2
通讯作者：
Peled N
中科院分区：
文献类型：
--
作者：
Shalata W;Iraqi M;Bhattacharya B;Fuchs V;Roisman LC;Cohen AY;Massalha I;Yakobson A;Prasad M;Elkabets M;Porgador A;Peled N
在过去的几十年里，强烈推荐使用多种药物治疗各种类型的癌症。本研究的目的是证明免疫检查点抑制剂 (ICIs) 和酪氨酸激酶抑制剂 (TKI) 的多种组合治疗不同癌症类型的优势。我们发现，与其他治疗相比，接受乐伐替尼和派姆单抗联合治疗的患者对治疗的反应增强。我们的离体研究表明，与未经处理的外植体或经单一处理的外植体相比，经过这种组合处理的 PDX 外植体的增殖和 PD-L1 水平降低。根据这项研究的结果，我们认为，正如最近的临床试验所表明的那样，levatinib 和 pembrolizumab 的组合作为非小细胞肺癌和恶性胸膜间皮瘤患者的治疗选择显示出巨大的潜力。癌症治疗的新时代使免疫检查点抑制剂（ICIs）和新兴的多激酶抑制剂（TKI）成为治疗标准，从而大大改善了患者的预后。 Pembrolizumab是一种抗程序性细胞死亡1抗体药物，lenvatinib是一种具有优先抗血管生成活性的TKI。据我们所知，我们首次报道了一系列病例，其中包括转移性非小细胞肺癌和恶性胸膜间皮瘤患者，他们接受了多种化疗组合和 ICI 治疗，随后出现疾病进展。随后，他们接受了联合免疫疗法和 TKI 治疗，在很短的时间内获得了接近完全的缓解。在目标癌细胞预先暴露于乐伐替尼后，通过体外测试每位患者对派姆单抗的淋巴细胞反应来支持临床反应。
Over the past decades, the multi-drug approach for treating various types of cancers was highly recommended. The aim of this study was to demonstrate the advantage of treating different carcinoma types with several combinations of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). We showed that patients treated with the combination of lenvatinib and pembrolizumab showed an enhanced response to therapy compared to other treatments. Our ex-vivo studies exhibited reduced proliferation and PD-L1 levels for PDX explants treated with this combination compared to untreated explants or those treated with a single treatment. Based on the results of this study, we propose that the combination of levatinib and pembrolizumab shows great potential as a treatment option for patients with non-small cell lung carcinoma and malignant pleural mesothelioma, as previously suggested by recent clinical trials. The new era of cancer treatments has made immune checkpoint inhibitors (ICIs) and emerging multikinase inhibitors (TKIs) the standards of care, thus drastically improving patient prognoses. Pembrolizumab is an anti-programmed cell death-1 antibody drug, and lenvatinib is a TKI with preferential antiangiogenic activity. We present, to our knowledge, the first reported series of cases consisting of patients with metastatic non–small cell lung cancer and malignant pleural mesothelioma who were treated with several types of chemotherapy combinations and ICIs followed by disease progression. They were subsequently treated with combined immunotherapy and TKI treatment, resulting in a near complete response within a very short time. Clinical responses were supported by in vitro testing of each patient’s lymphocytic response to pembrolizumab after pre-exposure of target cancer cells to lenvatinib.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
2.1
作者：
Tohyama O;Matsui J;Kodama K;Hata-Sugi N;Kimura T;Okamoto K;Minoshima Y;Iwata M;Funahashi Y
通讯作者：
Funahashi Y
影响因子：
45.3
作者：
Taylor, Matthew H.;Lee, Chung-Han;Motzer, Robert J.
通讯作者：
Motzer, Robert J.
影响因子：
4.7
作者：
Ghosh, Susmita;Prasad, Manu;Porgador, Angel
通讯作者：
Porgador, Angel
影响因子：
158.5
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
通讯作者：
Halmos, B