A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus).
A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus).
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DOI：
10.1038/bjc.2017.145
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发表时间：
2017-06-27
影响因子：
8.8
通讯作者：
Khemka V
中科院分区：
文献类型：
--
作者：
Weiss GJ;Waypa J;Blaydorn L;Coats J;McGahey K;Sangal A;Niu J;Lynch CA;Farley JH;Khemka V
Pembrolizumab (P)是一种抗PD-1抗体，可阻断t细胞上的程序性细胞死亡蛋白1 （PD-1）与肿瘤细胞上的PD-L1和PD-L2之间的相互作用。一项Ib期P +化疗试验进行了评估安全性和有效性。晚期转移性实体瘤患者被纳入六个治疗组中的一个。派姆单抗：与吉西他滨(G)、G+多西紫杉醇(D)、G+nab-紫杉醇（NP）、G+维诺瑞滨(V)或伊立替康(I)联用，直至进展或毒性，或与阿霉素脂质体（LD）联用长达15个周期、进展或毒性。进行了安全监测和反应评估。49名患者入组并接受治疗。最常见的不良反应是转氨炎、细胞减少、皮疹、腹泻、疲劳、恶心和呕吐。第2臂因应计收益不佳而关闭。第1、3a、4、5和6组的推荐II期剂量（RP2D）已确定。在多种肿瘤类型中有8种部分反应。标准剂量P可以安全地与G、G+NP、G+V、I和LD联合使用。在多种肿瘤类型中观察到疗效，评估反应和反应持续时间是否比单独化疗或免疫治疗更稳健，需要进一步验证。
Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy. Patients with advanced, metastatic solid tumours were enrolled onto one of six treatment arms. Pembrolizumab was given: with gemcitabine (G), G+docetaxel (D), G+nab-paclitaxel (NP), G+vinorelbine (V) or irinotecan (I) until progression or toxicity, or with liposomal doxorubicin (LD) for up to 15 cycles, progression or toxicity. Safety monitoring and response assessments were conducted. Forty-nine patients were enrolled and treated. The most common adverse events were transaminitis, cytopenias, rash, diarrhoea, fatigue, nausea and vomiting. Arm 2 was closed due to poor accrual. The recommended phase II dose (RP2D) was determined for Arms 1, 3a, 4, 5 and 6. There were eight partial responses across multiple tumour types. Standard dose P can be safely combined with G, G+NP, G+V, I and LD. Efficacy was observed in multiple tumour types and evaluation to determine if response and duration of response are more robust than what would be expected for chemotherapy or immunotherapy alone requires further validation.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1093/jnci/djp079
发表时间：
2009-05-20
期刊：
Journal of the National Cancer Institute
影响因子：
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DOI：
10.1126/science.aac4255
发表时间：
2015-11-27
期刊：
Science (New York, N.Y.)
影响因子：
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通讯作者：
Gajewski TF
影响因子：
45.3
作者：
Rizvi, Naiyer A.;Hellmann, Matthew D.;Antonia, Scott
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Antonia, Scott
DOI：
10.1016/j.jtho.2016.09.002
发表时间：
2017-01
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Yu H;Batenchuk C;Badzio A;Boyle TA;Czapiewski P;Chan DC;Lu X;Gao D;Ellison K;Kowalewski AA;Rivard CJ;Dziadziuszko R;Zhou C;Hussein M;Richards D;Wilks S;Monte M;Edenfield W;Goldschmidt J;Page R;Ulrich B;Waterhouse D;Close S;Jassem J;Kulig K;Hirsch FR
通讯作者：
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