Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People's Republic of China.
Department of Immunology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People's Republic of China.
Oncologist. 2021 Jul;26(7):e1110-e1124. doi: 10.1002/onco.13797. Epub 2021 Jun 5.
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.
放疗联合抗 PD-1 抗体作为一线治疗在局部晚期食管鳞状细胞癌（ESCC）中是安全且可行的。肿瘤浸润和外周淋巴细胞与患者生存相关。有必要进一步研究局部晚期 ESCC 中放化疗联合免疫治疗以及探索预测生物标志物。
我们开展了一项 Ib 期研究，评估放疗联合程序性死亡蛋白 1（PD-1）单克隆抗体卡瑞利珠单抗作为局部晚期食管鳞状细胞癌（ESCC）的一线治疗。
我们计划招募 20 例初诊局部晚期 ESCC 患者。患者接受 60 Gy 放疗（2.0 Gy/ 次，5 次/周），同时起始放疗即给予卡瑞利珠单抗（200 mg，每 2 周 1 次）治疗，共 32 周（即 16 个周期）。主要终点为安全性和可行性。次要终点为影像学和病理学缓解率、总生存期（OS）和无进展生存期（PFS）。研究数据在放疗（RT）期间每周、维持卡瑞利珠单抗治疗期间每月以及治疗后每 3 个月收集。在基线和 40 Gy 放疗后监测肿瘤微环境和外周血，以评估其与疗效的相关性。
共招募 20 例患者并接受治疗。1 例患者（患者 10）在治疗期间发现膀胱内有第二肿瘤，将其排除在外，19 例患者纳入分析。毒性可耐受。14 例（74%）患者可评估客观缓解。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 OS 和 PFS 率分别为 31.6%和 35.5%。Kaplan-Meier 分析显示，以下因素与 OS/PFS 相关：肿瘤程序性死亡配体 1（PD-L1）表达、PD-1 CD8+T 细胞、PD-1 CD4+T 细胞、PD-L1 CD4+T 细胞；外周血 CD4+、CD8+、CD4+调节性 T 细胞及其亚群。
放疗联合卡瑞利珠单抗治疗局部晚期 ESCC 的毒性可管理且具有抗肿瘤疗效。一些生物标志物与临床获益相关，值得进一步研究。
