Immune checkpoint inhibitors in NSCLC.
Immune checkpoint inhibitors in NSCLC.
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DOI：
10.1007/s11864-014-0305-5
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发表时间：
2014-12
影响因子：
4.3
通讯作者：
Horn, Leora
中科院分区：
文献类型：
--
作者：
Johnson, Douglas B.;Rioth, Matthew J.;Horn, Leora
关键词：
肺癌是全球癌症相关死亡的主要原因。细胞毒性化疗和酪氨酸激酶抑制剂提供了缓解和延长生存期，然而，转移性疾病患者的中位生存期仍然很差，需要更有效的治疗。免疫检查点抑制剂在I期试验中显示出有希望的结果，并正在小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）患者中进行临床试验。这些药物包括靶向程序性细胞死亡-1受体及其配体（PD-1/PD-L1;特别是纳武单抗、派姆单抗、MPDL 3280 A和MEDI-4736）和细胞毒性T淋巴细胞相关抗原4（CTLA-4;伊匹单抗和曲美木单抗）的药物;这些药物通过抑制关键的负性T细胞调节因子诱导抗肿瘤反应。特别是，在化疗难治性患者中作为单药治疗给予的抗PD-1/PD-L1治疗产生了15- 25%的客观缓解率，其中大多数在开始治疗后一年迅速且持续。此外，这些药物的毒性特征与细胞毒性化疗不同，但通常耐受性更好。有前景的生物标志物，特别是PD-L1和肿瘤浸润淋巴细胞的肿瘤表达，可能有助于治疗选择和分层。需要进行持续评估，以确定最合适的时机和患者人群，这些患者将受益于免疫检查点抑制剂治疗，以及将这些药物与现有治疗（包括全身治疗和放射治疗）结合的作用。
Lung cancer is the leading cause of cancer-related mortality worldwide. Cytotoxic chemotherapy and tyrosine kinase inhibitors provide palliation and prolong survival, however, the median survival for patients with metastatic disease remains poor and more effective therapies are needed. Immune checkpoint inhibitors have shown promising results in phase I trials and are being evaluated in ongoing clinical trials in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients. These include agents targeting the programmed cell death-1 receptor and its ligand (PD-1/PD-L1; notably nivolumab, pembrolizumab, MPDL3280A and MEDI-4736) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4; ipilimumab and tremelimumab); these agents induce antitumor responses by inhibiting critical negative T cell regulators. In particular, the anti-PD-1/PD-L1 therapies administered as single agent therapy in chemotherapy refractory patients have produced objective response rates ranging from 15–25%, the majority of which were rapid and ongoing one year after starting therapy. Furthermore, the toxicity profile for these agents differs from that of cytotoxic chemotherapy but generally is much better tolerated. Promising biomarkers, particularly tumor expression of PD-L1 and tumor infiltrating lymphocytes, may aid in treatment selection and stratification. Ongoing evaluation is needed to define the most appropriate timing and patient population that will benefit from therapy with an immune checkpoint inhibitors and the role of combining these agents with existing therapies including systemic therapy and radiation.
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影响因子：
10.1
作者：
Brahmer JR;Pardoll DM
通讯作者：
Pardoll DM
影响因子：
45.3
作者：
Lynch, Thomas J.;Bondarenko, Igor;Reck, Martin
通讯作者：
Reck, Martin
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
45.3
作者：
Scagliotti, Giorgio Vittorio;Parikh, Purvish;Gandara, David
通讯作者：
Gandara, David
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM