Efficacy, safety, and biomarker analysis of Camrelizumab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma (CAPTAIN study).
Efficacy, safety, and biomarker analysis of Camrelizumab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma (CAPTAIN study).
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DOI：
10.1136/jitc-2021-003790
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发表时间：
2021-12
影响因子：
10.9
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Yang Y;Zhou T;Chen X;Li J;Pan J;He X;Lin L;Shi YR;Feng W;Xiong J;Yang K;Yu Q;Zhang Q;Hu D;Sun Y;Hu G;Li P;Shen L;Lin Q;Zhang B;Qu X;Zou J;Zhang L;Fang W;Zhao Y
本研究旨在评估卡瑞利珠单抗（一种抗程序性细胞死亡 1 抗体）在预处理的复发性或转移性鼻咽癌 (NPC) 中的抗肿瘤活性，并探索预测生物标志物。至少两线化疗失败的复发性（不适合局部治愈性治疗）或转移性鼻咽癌患者有资格接受卡瑞利珠单抗（每两周静脉注射 200mg）2 年，或直至疾病进展、无法耐受的不良事件、撤回同意或研究者决定。主要终点是由独立审查委员会（IRC）评估的客观缓解率（ORR）。通过免疫组织化学评估程序性细胞死亡配体 1 (PD-L1) 的表达。通过多重免疫荧光染色评估其他免疫相关生物标志物，包括主要组织相容性复合物 I 类和主要组织相容性复合物 II 类 (MHC-II)。 2018年8月14日至2019年12月30日期间，共有156名患者入组。 IRC 评估的 ORR 为 28.2%（95% CI 21.3% 至 36.0%）。每个 IRC 的中位无进展生存期为 3.7 个月（95%CI 2.0 至 4.1），中位总生存期为 17.4 个月（95%CI 15.2 至 21.9）。肿瘤 PD-L1 表达≥10%和 <10% 的患者的 ORR 分别为 35.2%（95% CI 25.3% 至 46.1%）和 19.4%（95% CI 10.4% 至 31.4%）。具有持久临床获益（DCB）（定义为完全缓解、部分缓解或疾病稳定≥18周）的患者基质中MHC-II+细胞密度高于未获得DCB的患者（中位868.1（IQR 413.4-2854.0）细胞/mm2 vs 中位552.4（IQR 258.4至1242.1）细胞/mm2）。 MHC-II+ 细胞密度与 PD-L1 表达不相关，高基质 MHC-II+ 细胞密度和肿瘤 PD-L1 表达的复合物进一步丰富了可以从卡瑞利珠单抗中受益的患者。卡瑞利珠单抗对复发性或转移性鼻咽癌患者具有临床意义的抗肿瘤活性。 MHC-II+ 细胞密度和 PD-L1 表达的组成可以导致更好的患者选择。
This study aimed to evaluate the antitumor activity of camrelizumab, an antiprogrammed cell death-1 antibody, in pretreated recurrent or metastatic nasopharyngeal carcinoma (NPC) and to explore predictive biomarkers. Patients with recurrent (not amenable to locally curative treatment) or metastatic NPC who had failed at least two lines of chemotherapy were eligible to receive camrelizumab (200 mg intravenously every 2 weeks) for 2 years or until disease progression, intolerable adverse events, withdrawal of consents, or investigator decision. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC). Programmed cell death-ligand 1 (PD-L1) expression was assessed by immunohistochemistry. Other immune-related biomarkers including major histocompatibility complex class I and major histocompatibility complex class II (MHC-II) were assessed by multiplex immunofluorescence staining. Between August 14, 2018, and December 30, 2019, a total of 156 patients were enrolled. The IRC-assessed ORR was 28.2% (95% CI 21.3% to 36.0%). The median progression-free survival was 3.7 months (95% CI 2.0 to 4.1) per IRC, and the median overall survival was 17.4 months (95% CI 15.2 to 21.9). The ORRs were 35.2% (95% CI 25.3% to 46.1%) vs 19.4% (95% CI 10.4% to 31.4%) in patients with tumor PD-L1 expression of ≥10% and<10%, respectively. Patients with durable clinical benefit (DCB), which was defined as complete response, partial response or stable disease of ≥18 weeks, had higher density of MHC-II+ cell in stroma than patients without DCB (median 868.1 (IQR 413.4–2854.0) cells/mm2 vs median 552.4 (IQR 258.4 to 1242.1) cells/mm2). MHC-II+ cell density did not correlate with PD-L1 expression, and a composite of high stromal MHC-II+ cell density and tumor PD-L1 expression further enriched patients who could benefit from camrelizumab. Camrelizumab had clinically meaningful antitumor activity in patients with recurrent or metastatic NPC. The composition of both MHC-II+ cell density and PD-L1 expression could result in better patient selection.
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影响因子：
45.3
作者：
Hsu, Chiun;Lee, Se-Hoon;Hansen, Aaron R.
通讯作者：
Hansen, Aaron R.
影响因子：
45.3
作者：
Ma, Brigette B. Y.;Lim, Wan-Teck;Chan, Anthony T. C.
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Chan, Anthony T. C.
影响因子：
20.3
作者：
Lin, Jiun-Han;Lin, Ju-Yin;Tsai, Ching-Hwa
通讯作者：
Tsai, Ching-Hwa
影响因子：
4.4
作者：
Li, Dan;Qian, Lu;Guo, Ning
通讯作者：
Guo, Ning
影响因子：
16.6
作者：
Johnson DB;Estrada MV;Salgado R;Sanchez V;Doxie DB;Opalenik SR;Vilgelm AE;Feld E;Johnson AS;Greenplate AR;Sanders ME;Lovly CM;Frederick DT;Kelley MC;Richmond A;Irish JM;Shyr Y;Sullivan RJ;Puzanov I;Sosman JA;Balko JM
通讯作者：
Balko JM