Safety and Feasibility of Radiotherapy Plus Camrelizumab for Locally Advanced Esophageal Squamous Cell Carcinoma.
Safety and Feasibility of Radiotherapy Plus Camrelizumab for Locally Advanced Esophageal Squamous Cell Carcinoma.
复制标题
放疗加卡瑞利珠单抗治疗局部晚期食管鳞状细胞癌的安全性和可行性
DOI：
10.1002/onco.13797
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Pang Q
中科院分区：
文献类型：
--
作者：
Zhang W;Yan C;Gao X;Li X;Cao F;Zhao G;Zhao J;Er P;Zhang T;Chen X;Wang Y;Jiang Y;Wang Q;Zhang B;Qian D;Wang J;Zhou D;Ren X;Yu Z;Zhao L;Yuan Z;Wang P;Pang Q
放射治疗加抗PD-1抗体作为一线治疗对于局部晚期食管鳞状细胞癌（ESCC）是安全可行的。肿瘤浸润和外周淋巴细胞与患者生存相关。有必要对局部晚期 ESCC 进行放化疗与免疫治疗相结合的进一步研究，并探索预测性生物标志物。我们进行了放疗联合程序性细胞死亡蛋白 1 (PD-1) 单克隆抗体 camrelizumab 作为局部晚期食管鳞状细胞癌 (ESCC) 一线治疗的 Ib 期研究。我们计划招募 20 名新诊断的局部晚期 ESCC 患者。患者接受 60 Gy 放射（2.0 Gy/分次，5 次/周），并使用卡瑞利珠单抗（每 2 周 200 mg），从放疗开始持续 32 周（即 16 个周期）。主要终点是安全性和可行性。次要终点是放射学和病理学反应率、总生存期（OS）和无进展生存期（PFS）。研究数据在放疗 (RT) 期间按周收集、卡瑞利珠单抗维持治疗期间每月收集一次、治疗后每 3 个月收集一次。在基线和 40 Gy 辐射后监测肿瘤微环境和外周血，以与疗效相关。二十名患者入组并接受治疗。一名患者（患者 10）因在治疗期间发现膀胱中出现第二个肿瘤而被排除，留下 19 名患者进行分析。毒性被认为是可以忍受的。十四名 (74%) 患者评估了客观反应。中位随访时间为 31.0 个月（95% 置信区间 [CI]，27.0-35.1），中位 OS 和 PFS 时间分别为 16.7 个月（95% CI，5.9-27.9）和 11.7 个月（95% CI，0-30.3）。 24 个月时的 OS 和 PFS 率分别为 31.6% 和 35.5%。 Kaplan-Meier 分析揭示了以下因素与 OS/PFS 之间的关联：肿瘤程序性细胞死亡配体 1 (PD-L1) 表达、PD-1+CD8+、PD-1+CD4+ T 细胞和 PD-L1+CD4+ T 细胞；外周血 CD4+、CD8+、CD4+ 调节性 T 细胞及其亚群。放疗加卡瑞利珠单抗对于局部晚期 ESCC 具有可控的毒性和抗肿瘤功效。一些生物标志物与临床获益相关，值得进一步研究。
Radiotherapy plus anti–PD‐1 antibody as first‐line therapy is safe and feasible in locally advanced esophageal squamous cell carcinoma (ESCC). Tumor‐infiltrating and peripheral lymphocytes were associated with patient survival. Further studies combining chemoradiotherapy with immunotherapy in locally advanced ESCC and exploration of predictive biomarkers are warranted. We conducted a phase Ib study of radiotherapy plus programmed cell death protein 1 (PD‐1) monoclonal antibody camrelizumab as first‐line treatment for locally advanced esophageal squamous cell carcinoma (ESCC). We planned to enroll 20 patients with newly diagnosed locally advanced ESCC. Patients received 60 Gy radiation (2.0 Gy/fraction, 5 fractions/week), with camrelizumab (200 mg every 2 weeks) starting with radiotherapy and continuing for 32 weeks (i.e., for 16 cycles). The primary endpoints were safety and feasibility. Secondary endpoints were rates of radiologic and pathologic response, overall survival (OS), and progression‐free survival (PFS). Study data were collected by the week during radiotherapy (RT), every month during the maintenance camrelizumab treatment, and every 3 months after treatment. Tumor microenvironment and peripheral blood were monitored at baseline and after 40 Gy radiation for association with efficacy. Twenty patients were enrolled and received treatment. One patient (patient 10) was excluded upon discovery of a second tumor in the bladder during treatment, leaving 19 patients for analysis. Toxicity was deemed tolerable. Fourteen (74%) patients had assessed objective response. At a median follow‐up time of 31.0 months (95% confidence interval [CI], 27.0–35.1), median OS and PFS times were 16.7 months (95% CI, 5.9–27.9) and 11.7 months (95% CI, 0–30.3), respectively. OS and PFS rates at 24 months were 31.6% and 35.5%, respectively. Kaplan‐Meier analysis revealed associations between the following factors and OS/PFS: tumor programmed cell death ligand 1 (PD‐L1) expression, PD‐1+CD8+, PD‐1+CD4+ T cells, and PD‐L1+CD4+ T cells; peripheral blood CD4+, CD8+, CD4+ regulatory T cells, and their subsets. Radiotherapy plus camrelizumab had manageable toxicity and antitumor efficacy for locally advanced ESCC. Several biomarkers were associated with clinical benefit and deserve further study.
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影响因子：
64.8
作者：
Simoni, Yannick;Becht, Etienne;Newell, Evan W.
通讯作者：
Newell, Evan W.
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45.3
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Doi, Toshihiko;Piha-Paul, Sarina A.;Bennouna, Jaafar
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Bennouna, Jaafar
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28.4
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Suntharalingam, Mohan;Winter, Kathryn;Crane, Christopher H.
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Crane, Christopher H.
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51.1
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Kudo, Toshihiro;Hamamoto, Yasuo;Kitagawa, Yuko
通讯作者：
Kitagawa, Yuko
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64.8
作者：
Twyman-Saint Victor, Christina;Rech, Andrew J.;Maity, Amit;Rengan, Ramesh;Pauken, Kristen E.;Stelekati, Erietta;Benci, Joseph L.;Xu, Bihui;Dada, Hannah;Odorizzi, Pamela M.;Herati, Ramin S.;Mansfield, Kathleen D.;Patsch, Dana;Amaravadi, Ravi K.;Schuchter, Lynn M.;Ishwaran, Hemant;Mick, Rosemarie;Pryma, Daniel A.;Xu, Xiaowei;Feldman, Michael D.;Gangadhar, Tara C.;Hahn, Stephen M.;Wherry, E. John;Vonderheide, Robert H.;Minn, Andy J.
通讯作者：
Minn, Andy J.