可切除 NSCLC 患者新辅助卡瑞利珠单抗联合阿帕替尼的疗效、安全性及生物标志物分析：一项 2 期临床试验。

Efficacy, Safety, and Biomarker Analysis of Neoadjuvant Camrelizumab and Apatinib in Patients With Resectable NSCLC: A Phase 2 Clinical Trial.

机构信息

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

出版信息

J Thorac Oncol. 2023 Jun;18(6):780-791. doi: 10.1016/j.jtho.2023.02.019. Epub 2023 Mar 2.

DOI:10.1016/j.jtho.2023.02.019

PMID:36870519

Abstract

INTRODUCTION

Camrelizumab (an anti-programmed cell death protein-1 antibody) combined with apatinib (an antiangiogenic agent) has conferred benefits for advanced NSCLC. We aimed to assess the activity and safety of neoadjuvant camrelizumab plus apatinib in patients with resectable NSCLC.

METHODS

In this phase 2 trial, patients with histologically confirmed resectable stages IIA to IIIB NSCLC (stage IIIB, T3N2 only) received intravenous camrelizumab (200 mg) every 2 weeks for three cycles and oral apatinib (250 mg) once daily for 5 days followed by 2 days off for 6 weeks. Surgery was planned 3 to 4 weeks after apatinib discontinuation. The primary end point was major pathologic response (MPR) rate, assessed in patients who received at least one dose of neoadjuvant treatment and underwent surgery.

RESULTS

Between November 9, 2020, and February 16, 2022, 78 patients were treated and 65 (83%) underwent surgery. All 65 patients achieved an R0 surgical resection. Among the 65 patients, 37 (57%, 95% confidence interval [CI]: 44%-69%) had an MPR, of whom 15 (23%, 95% CI: 14%-35%) had a pathologic complete response (pCR). Pathologic responses observed in squamous cell NSCLC were superior to adenocarcinoma (MPR: 64% versus 25%; pCR: 28% versus 0%). The radiographic objective response rate was 52% (95% CI: 40%-65%). Among all the 78 enrolled patients, 37 (47%, 95% CI: 36%-59%) had an MPR, of whom 15 (19%, 95% CI: 11%-30%) had a pCR. Four (5%) of 78 patients had grade 3 neoadjuvant treatment-related adverse events. No grade 4 or 5 treatment-related adverse events occurred. Receiver operating characteristic analysis revealed a significant correlation between the maximum reduction of standard uptake values and pathologic response (R = 0.619, p < 0.0001). In addition, baseline programmed death-ligand 1 expression, HOXA9 and SEPT9 methylation levels, and circulating tumor DNA status before surgery were associated with pathologic responses.

CONCLUSIONS

Neoadjuvant camrelizumab plus apatinib was found to have promising activity and manageable toxicity in patients with resectable stages IIA to IIIB NSCLC, which might be a potential therapeutic option in neoadjuvant setting.

摘要

简介

卡瑞利珠单抗（一种抗程序性死亡蛋白-1 抗体）联合阿帕替尼（一种抗血管生成药物）可使晚期 NSCLC 患者获益。我们旨在评估可切除 NSCLC 患者新辅助卡瑞利珠单抗联合阿帕替尼的疗效和安全性。

方法

在这项 2 期临床试验中，组织学证实可切除 IIA 至 IIIB 期 NSCLC（III 期 B，仅 T3N2）的患者接受静脉注射卡瑞利珠单抗（200mg）每 2 周 3 个周期，同时每日口服阿帕替尼（250mg）连用 5 天，停药 2 天，共 6 周。阿帕替尼停药后 3 至 4 周进行手术。主要终点是评估至少接受一剂新辅助治疗且接受手术的患者的主要病理缓解（MPR）率。

结果

2020 年 11 月 9 日至 2022 年 2 月 16 日，共 78 例患者接受治疗，65 例（83%）接受手术。所有 65 例患者均行 R0 手术切除。在 65 例患者中，37 例（57%，95%置信区间：44%-69%）有 MPR，其中 15 例（23%，95%置信区间：14%-35%）达到病理完全缓解（pCR）。鳞状细胞 NSCLC 的病理缓解优于腺癌（MPR：64%比 25%；pCR：28%比 0%）。所有 78 例入组患者的放射学客观缓解率为 52%（95%置信区间：40%-65%）。在所有 78 例入组患者中，37 例（47%，95%置信区间：36%-59%）有 MPR，其中 15 例（19%，95%置信区间：11%-30%）达到 pCR。78 例患者中有 4 例（5%）出现 3 级新辅助治疗相关不良事件。无 4 级或 5 级治疗相关不良事件发生。受试者工作特征分析显示，标准摄取值最大降低与病理反应之间存在显著相关性（R=0.619，p<0.0001）。此外，基线程序性死亡配体 1 表达、HOXA9 和 SEPT9 甲基化水平以及手术前的循环肿瘤 DNA 状态与病理反应相关。