卡瑞利珠单抗联合阿帕替尼和替吉奥二线治疗晚期胃或胃食管结合部腺癌的Ⅱ期单臂前瞻性研究。
Camrelizumab combined with apatinib and S-1 as second-line treatment for patients with advanced gastric or gastroesophageal junction adenocarcinoma: a phase 2, single-arm, prospective study.
机构信息
Department of General Surgery, Medical Oncology Group, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences/China National Center for Bioinformation, Beijing, 100101, China.
出版信息
Cancer Immunol Immunother. 2022 Nov;71(11):2597-2608. doi: 10.1007/s00262-022-03174-9. Epub 2022 Mar 18.
BACKGROUND
The current second-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma remains unsatisfactory. Anti-PD-1 monoclonal antibody combined with anti-angiogenic therapy shows anti-tumor activity and synergistic effect. We aimed to assess the efficacy and safety of the combination therapy of camrelizumab, apatinib, and S-1 in patients with gastric or gastroesophageal junction adenocarcinoma.
METHODS
In this open-label, single-arm, phase 2 trial, in each 21-day cycle, eligible patients received 200 mg intravenous camrelizumab in the first day, 500 mg oral apatinib once daily continuously, and specific dose oral S-1 in the first 14 days until the trial was discontinued disease progression, development of intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response rate. The secondary endpoints were disease control rate, progression-free survival and overall survival, and safety. This study was registered at ClinicalTrials.gov, NCT04345783.
RESULTS
Between May 2019 and August 2020, we enrolled a total of 24 patients in this trial. At the data cutoff (December 1, 2020), the median follow-up duration was 8.13 months. Seven of 24 (29.2%, 95%CI 14.9-49.2%) patients reached objective response. The median-progression-free survival was 6.5 months (95%CI 6.01-6.99) and the median overall survival was not reached. Grade 3 or 4 adverse events occurred in 6 (25.0%) patients, including elevated transaminase, thrombocytopenia, fatigue, proteinuria, and intestinal obstruction. No serious treatment-related adverse events or treatment-related deaths occurred.
CONCLUSIONS
In this trial, the combination of camrelizumab, apatinib, and S-1 showed promising anti-tumor activity and manageable toxicity as a second-line therapy in patients with advanced gastric or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression.
CLINICAL TRIAL REGISTRATION
NCT04345783.
背景
晚期胃或胃食管结合部腺癌的二线治疗仍不尽人意。抗 PD-1 单克隆抗体联合抗血管生成治疗显示出抗肿瘤活性和协同作用。我们旨在评估卡瑞利珠单抗、阿帕替尼和 S-1 联合治疗胃或胃食管结合部腺癌患者的疗效和安全性。
方法
在这项开放标签、单臂、2 期试验中，在每个 21 天的周期中，符合条件的患者在第 1 天接受 200mg 静脉注射卡瑞利珠单抗，每天口服 500mg 阿帕替尼连续治疗，以及在第 14 天口服特定剂量的 S-1，直至试验因疾病进展、不可耐受毒性的发展或患者撤回同意而停止。主要终点是客观缓解率。次要终点是疾病控制率、无进展生存期和总生存期以及安全性。本研究在 ClinicalTrials.gov 注册，NCT04345783。
结果
2019 年 5 月至 2020 年 8 月期间，我们共纳入了 24 名患者参加了这项试验。在数据截止日期（2020 年 12 月 1 日），中位随访时间为 8.13 个月。24 名患者中有 7 名（29.2%，95%CI 14.9-49.2%）达到客观缓解。中位无进展生存期为 6.5 个月（95%CI 6.01-6.99），中位总生存期未达到。6 名（25.0%）患者发生 3 级或 4 级不良事件，包括转氨酶升高、血小板减少、疲劳、蛋白尿和肠梗阻。无严重治疗相关不良事件或治疗相关死亡。
结论
在这项试验中，卡瑞利珠单抗、阿帕替尼和 S-1 联合治疗作为晚期胃或胃食管结合部腺癌二线治疗，无论 PD-L1 表达情况如何，均显示出有希望的抗肿瘤活性和可管理的毒性。
临床试验注册
NCT04345783。
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