卡瑞利珠单抗联合阿帕替尼、白蛋白紫杉醇及替吉奥用于进展期胃癌的转化治疗

Camrelizumab,apatinib,nab-paclitaxel,and S-1 in combination for the conversion therapy of advanced gastric cancer

目的旨在评估卡瑞利珠单抗、阿帕替尼、白蛋白紫杉醇和替吉奥四药联用作为进展期胃癌转化治疗的有效性及安全性。方法本研究为前瞻性单臂研究。收集2019年9月1日—2021年8月1日于首都医科大学附属北京友谊医院纳入的进展期胃癌患者17例。入组患者均接收卡瑞利珠单抗+白蛋白紫杉醇+阿帕替尼+替吉奥治疗(每3周为1个治疗周期,卡瑞利珠单抗200 mg静脉注射,第1天;白蛋白紫杉醇240 mg/m2静脉注射,第2天;阿帕替尼500 mg口服,每日1次,第1天至第21天;替吉奥40~60 mg,每日2次,第1天至第14天)。经多学科联合会诊评估为可R0切除者,则需停药至少2周,并接受根治性胃癌切除术。当出现疾病进展,或出现难以忍受的毒性,或者患者撤回同意,或接受转化治疗,则退出研究。主要分析患者转化率、客观缓解率(ORR)、疾病控制率(DCR)、总生存期(OS)和安全性。计数资料用例和百分率(%)表示,亚组间比较采用Fisher精确概率法。患者生存采用Kaplan-Meier曲线进行分析,采用Log-rank进行组间比较。结果在数据截止日期(2021年12月15日),中位随访期为19.5个月。17例患者中8例接受治疗后成功进行了手术(转化率为47.1%,95%CI:0.262~0.690),且均为R0切除。治疗的ORR为47.1%(8/17),DCR达82.4%,中位总体生存期为23.63个月。3例(17.6%)患者发生3级不良事件,包括转氨酶升高、血小板减少、疲劳、蛋白尿、肠梗阻等。未发生严重的治疗相关不良事件或治疗相关死亡。结论在晚期胃癌患者中,卡瑞利珠单抗、阿帕替尼、白蛋白紫杉醇和替吉奥联合作为局部不可切除晚期胃癌患者的转化治疗,显示出显著的抗肿瘤活性和可控制的毒性,为转化治疗提供新的药物治疗方案选择。

Objective To assess the efficacy and safety of the combination therapy of camrelizumab,apatinib,nab-paclitaxel,and S-1 for patients with locally unresectable advanced gastric cancer.Methods From September 1,2019 to August 1,2021,in Beijing Friendship Hospital Affiliated to Capital Medical University,17 patients with advanced gastric cancer were enrolled in this prospective,single-arm study.All the enrolled patients received camrelizumab,nab-paclitaxel,apatinib and S-1 combination therapy(in each 21 days cycle,camrelizumab 200 mg intravenously,D1;nab-paclitaxel 240 mg/m2 intravenously,D2;apatinib 500 mg orally,once a day,D1-D21;S-140-60 mg twice a day,D1-D14).Patients who have been evaluated by multidisciplinary team to be eligible for radical surgery should stop treatment for at least 2 weeks.Patients were discontinued from the study when disease progression or unbearable toxicity,or withdrew consent.We analyzed the conversion rate,objective response rate(ORR),disease control rate(DCR),overall survival(OS)and safety.Statistical data were show by numbers and persentages(%),and comparisons between subgroups were assessed by Fisher′s exact probability method.Patients survival was analyzed using Kaplan-Meier curves and compared between groups using Log-rank.Results At the data of cutoff(December 15,2021),the median follow-up duration was 19.6 months.Eight of 17 patients underwent gastrectomy,and all of them were R0 resection(47.1%,95%CI:0.262-0.690).ORR was 47.1%,DCR was 82.4%,the median overall survival was 23.63 months.Grade 3 and 4 adverse events occurred in 3 patients(17.6%),including neutropenia,thrombocytopenia,anemia and upper gastrointestinal hemorrhage.There were no serious treatment-related adverse events or treatment-related deaths.Conclusion In this trial,the combination of camrelizumab,apatinib,nab-paclitaxel and S-1 as the conversion therapy showed significant anti-tumor activity and manageable adverse events,providing a new option for locally unresectable advanced gastric cancer.