卡瑞利珠单抗联合诱导化疗后放化疗治疗局部晚期鼻咽癌的疗效

目的探讨卡瑞利珠单抗联合诱导化疗后序贯同步放化疗在局部晚期鼻咽癌患者中的临床效果和安全性。方法前瞻性纳入Ⅲ～IVA期鼻咽癌患者共24例, 接受两周期卡瑞利珠单抗(200 mg)联合多西他赛+顺铂诱导化疗(多西他赛75 mg/m2+顺铂25 mg/m2连续3 d), 之后接受标准同步放化疗(处方剂量:PGTV、PGTVnd为6 996 cGy/33次、PTV1为6 006 cGy/33次、PTV2为5 096 cGy/28次, 同步顺铂化疗, 剂量为75 mg/m2)。观察患者的近期疗效和不良反应。结果诱导治疗后鼻咽病灶客观缓解率(ORR)为91.6%[完全缓解(CR)45.8%+部分缓解(PR)45.8%];颈部淋巴结ORR为95.8%(CR 4.2%, PR 91.6%)。17例同意复查鼻咽镜, 咬检后显示13例获得病理完全缓解。同步放化疗后鼻咽病灶CR为83.3%, PR为16.7%;颈部淋巴结CR为91.7%, PR为8.3%。13例IVA期患者诱导治疗后鼻咽病灶ORR为92.4%, 颈部淋巴结ORR为92.4%, 均为PR。同步放化疗结束后鼻咽病灶CR为84.6%, PR为15...     

卡瑞利珠单抗联合化疗治疗中国晚期非小细胞肺癌的成本-效果分析

摘 要 目的：评价卡铂和培美曲塞联合卡瑞利珠单抗与单独化疗用于晚期非鳞状非小细胞肺癌（NSCLC）的成本-效果分析。方法：建立Markov模型,对卡瑞利珠单抗联合化疗与单独化疗一线治疗晚期非鳞状NSCLC进行成本-效果分析。临床效果参数和效用参数源于Ⅲ期临床试验（CameL试验）数据和国内外参考文献,结果指标包括成本、质量调整生命年（QALYs）和增量成本-效果比（ICER）。采用单因素和概率敏感性分析对结果进行分析,以评估模型结果的稳健性。结果：基础分析显示,卡瑞利珠单抗联合化疗可产生额外的0.395 QALY,增量成本为48 786元,从卫生体系角度来看,对应于每个QALY的增量成本效益比为123 509元。从医保支付方角度作情境分析,结果显示,从城镇居民医保角度卡瑞利珠单抗化疗的ICER为101 959元,从职工医保角度ICER为103 393元。结论：基于217 341元/QALY的支付意愿阈值,对于中国晚期非鳞状NSCLC患者,卡瑞利珠单抗联合化疗的一线治疗相对于单独化疗具有经济学优势。     

安罗替尼对卡瑞利珠单抗在治疗进展期非小细胞肺癌中引起反应性毛细血管增生症的缓解作用分析

目的：探讨安罗替尼对卡瑞利珠单抗在治疗进展期非小细胞肺癌（NSCLC）中引起反应性毛细血管增生症（RCHs）的缓解作用。方法：纳入136例使用卡瑞利珠单抗治疗的进展期NSCLC患者，随机分为卡瑞利珠单抗 + 安罗替尼组（观察组，73例）和卡瑞利珠单抗+安慰剂组（对照组，63例）。两组均随访25周，每用药2个周期（42天）评价一次疗效和安全性，主要指标包括发病时间、持续时间和严重程度。结果：79例（58.09%）患者出现RCHs，其中观察组31例（42.47%），对照组48例（76.19%），观察组RCHs发生率显著低于对照组，差异有统计学意义（P ＜ 0.001）。观察组RCHs的出现时间迟于对照组，消退时间则短于对照组，差异有统计学意义（P ＜ 0.001）。两组RCHs严重程度比较，差异无统计学意义（P = 0.721）。结论：RCHs是卡瑞利珠单抗治疗的进展期NSCLC患者中常见的皮肤毒性反应，联合安罗替尼可降低卡瑞利珠单抗相关RCHs的发生率并诱导其快速消退。     

卡瑞利珠单抗联合阿帕替尼致严重皮肤不良反应1例★

1例80岁男性患者因左肺腺癌行6周期化疗后进展，采用免疫治疗，给予卡瑞利珠单抗0.2 g静脉滴注（d1，21 d为1个周期）。首次静脉滴注卡瑞利珠单抗后1周，患者躯干部出现多处皮疹伴瘙痒，对症治疗后好转。继续第2周期卡瑞利珠单抗联合阿帕替尼治疗后5 d，患者头面部、躯干及四肢再次出现大面积皮疹伴瘙痒，诊断为发疹型药疹。停用卡瑞利珠单抗及阿帕替尼，给予糖皮质激素和抗过敏药物等治疗，10 d后皮疹基本消退。     

卡瑞利珠单抗,一种人源化抗PD-1 IgG4亚型单克隆抗体在临床前研究中表现出优异的抗肿瘤活性以及良好的安全性

卡瑞利珠单抗是一种人源化的抗PD-1单克隆抗体.在体外与人和食蟹猴PD-1蛋白具有纳摩尔级别的高亲和力,但不结合鼠源PD-1蛋白.它在体外有效阻断PD-1/PD-L1信号通路的同时还可以激活T细胞.卡瑞利珠单抗与PD-1独特的结合表位同PD-1和PD-L1结合表位有部分的重叠,证明了卡瑞利珠单抗对PD-1/PD-L1具...     

1例卡瑞利珠单抗致重度心肌炎不良反应及临床分析

免疫检查点抑制剂在临床的使用范围逐渐扩大,可明显延长患者生存期,但其独特的免疫相关不良反应也应该引起人们的重视。本文分析1例61岁晚期肺癌女性患者使用卡瑞利珠单抗（200 mg,ivgtt q2w）12天后,出现头晕并逐渐加重,考虑为PD-1抑制剂引起的免疫相关性肌炎累及心肌、伴横纹肌溶解的重叠综合征,予以激素冲击联合免疫球蛋白抗炎及其他对症治疗,但最终结局并未好转。     

Safety and Feasibility of Radiotherapy Plus Camrelizumab for Locally Advanced Esophageal Squamous Cell Carcinoma

Lessons Learned

• 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.

BackgroundWe 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).MethodsWe 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.ResultsTwenty 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.ConclusionRadiotherapy plus camrelizumab had manageable toxicity and antitumor efficacy for locally advanced ESCC. Several biomarkers were associated with clinical benefit and deserve further study.     

卡瑞利珠单抗联合化疗方案对中晚期食管癌患者血清miR-21、可溶性E-钙黏蛋白表达的影响

目的 探讨卡瑞利珠单抗联合化疗方案对中晚期食管癌患者血清miR-21、可溶性E-钙黏蛋白（sE-Cad）表达的影响。方法 中晚期食管癌患者110例按用药方案不同分为联合组（57例）和化疗组（53例）。化疗组患者接受紫杉醇（260 mg/m²）+顺铂（30 mg/m²）方案治疗,联合组在此基础上接受卡瑞利珠单抗（200 mg/次,1次/2周）治疗。治疗4~6个周期后,评估2组总体疗效;酶联免疫吸附试验法检测血清肿瘤标志物、sE-Cad水平,实时荧光定量聚合酶链反应检测血清miR-21水平;记录治疗期间不良反应发生情况。结果 治疗后,联合组患者的客观有效率（ORR）为70.18%,疾病控制率（DCR）为91.23%,高于化疗组的45.28%和77.36%（P<0.05）;治疗后联合组血清糖类抗原125（CA125）、癌胚抗原（CEA）、鳞状细胞癌相关性抗原（SCC）、miR-21和sE-Cad水平均明显低于化疗组（P<0.05）;治疗期间,联合组的反应性毛细血管增生症发生率高于化疗组（P<0.01）。结论 卡瑞利珠单抗联合化疗方案治疗中晚期食管癌近期疗效良好,可有效降低肿瘤标志物水平,下调miR-21、sE-Cad在血清中的表达。