肿瘤细胞治疗研究
英文原题：Camrelizumab, chemotherapy and apatinib in the neoadjuvant treatment of resectable oesophageal squamous cell carcinoma: a single-arm phase 2 trial.
在这项单臂研究中，卡瑞利珠单抗、化疗与阿帕替尼用于局部晚期食管鳞癌（ESCC）的新辅助治疗显示出良好的抗肿瘤活性和可接受的安全性。
背景：在可切除食管鳞状细胞癌（ESCC）中，卡瑞利珠单抗联合化疗和阿帕替尼后进行微创食管切除术的疗效尚不明确。本研究旨在弥补这一认识空白。 方法：这项研究者发起的单臂前瞻性II期试验在中国浙江大学医学院附属第二医院开展。组织学或细胞学确诊ESCC、年龄18–75岁的患者可入组。患者接受2–3个周期新辅助治疗，包括卡瑞利珠单抗、奈达铂、白蛋白紫杉醇和阿帕替尼，每周期14天。末次新辅助治疗后4–6周进行手术。主要结局为肿瘤和淋巴结病理完全缓解（pCR）率。通过质谱流式细胞术评估未达到pCR（NPCR）和达到pCR患者外周血免疫谱变化。试验注册号：ClinicalTrials.gov，NCT04666090。 结果：2020年11月23日至2022年12月31日共入组42例患者。疾病控制率为100.0%（95% CI 91.6–100%），客观缓解率为83.3%（95% CI 68.6–93.0%）。6例（14.3%）患者发生3级不良事件。最常见事件包括白细胞计数下降（31.0%）、脱发（81.0%）、乏力（38.1%）及反应性皮肤毛细血管内皮增生（35.7%）。41例接受微创食管切除术，均达到R0切除；其中18例（43.9%，95% CI 28.5–60.3%）达到pCR。中位随访23个月，2年生存率为85.9%。pCR组和NPCR组的T细胞亚群对新辅助治疗的应答模式相似。相较之下，部分NK细胞（NK-C03、NK-C11）、B细胞（B-C06）和单核细胞（M-C05）亚群在新辅助治疗前两组间差异显著；治疗后M-C06在两组间差异显著；NK-C12和B-C15在治疗前后均存在显著差异。 解释：在这项单臂研究中，局部晚期ESCC新辅助应用卡瑞利珠单抗、化疗和阿帕替尼显示出有前景的抗肿瘤活性和可接受的安全性。在新辅助治疗情境下，NK细胞、B细胞和单核细胞亚群对免疫治疗应答的预测能力高于T细胞亚群。仍需延长随访以评估生存结局，并开展III期随机试验进一步评价该方案。 经费：中国抗癌协会和浙江省“领雁”研发攻关计划。
BACKGROUND: In resectable oesophageal squamous cell carcinoma (ESCC), the efficacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fill this knowledge gap. METHODS: This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Affiliated Hospital of Zhejiang University, China. Patients (aged 18-75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2-3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4-6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunoprofile among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. FINDINGS: 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6-100%), and the objective response rate was 83.3% (95% CI, 68.6-93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5-60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B-C06) and monocytes (M-C05), exhibited significant differences between the PCR and NPCR groups before neoadjuvant therapy. M-C06 had a significant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B-C15 showed significant differences both before and after neoadjuvant therapy. INTERPRETATION: The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety profile in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment. FUNDING: The China Anti-Cancer Association and the "Leading Goose" Research and Development Project of Zhejiang Province.
MEMBER ACCOUNT
登录成功会直接打开下一页。
