Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma

Cancer Communications

article

Bo Zhang¹  Ling Qi¹  Xi Wang¹  Jianping Xu¹  Yun Liu¹  Lan Mu¹  Xingyuan Wang¹  Lidan Bai³  Jing Huang¹ 

[1] Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;BZ and LQ contributed equally to this work.;Jiangsu Hengrui Medicine Co. Ltd.

关键词: anti-angiogenesis;    apatinib;    camrelizumab;    chemotherapy;    esophageal squamous cell carcinoma;    first-line;    immunotherapy;    liposomal paclitaxel;    nedaplatin;    objective response rate;   

DOI  :  10.1002/cac2.12119

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 摘 要 】

Background Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma (ESCC). The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects. Therefore, we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC. Methods In this single-arm prospective phase II trial, patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg, liposomal paclitaxel 150 mg/m 2 , and nedaplatin 50 mg/m 2 on day 1, and apatinib 250 mg on days 1-14. The treatments were repeated every 14 days for up to 9 cycles, followed by maintenance therapy with camrelizumab and apatinib. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results We enrolled 30 patients between August 7, 2018 and February 23, 2019. The median follow-up was 24.98 months (95% confidence interval [CI]: 23.05-26.16 months). The centrally assessed ORR was 80.0% (95% CI: 61.4%-92.3%), with a median duration of response of 9.77 months (range: 1.54 to 24.82+ months). The DCR reached 96.7% (95% CI: 82.8%-99.9%). The median PFS was 6.85 months (95% CI: 4.46-14.20 months), and the median OS was 19.43 months (95% CI: 9.93 months – not reached). The most common grade 3-4 treatment-related adverse events (AEs) were leukopenia (83.3%), neutropenia (60.0%), and increased aspartate aminotransferase level (26.7%). Treatment-related serious AEs included febrile neutropenia, leukopenia, and anorexia in one patient (3.3%), and single cases of increased blood bilirubin level (3.3%) and toxic epidermal necrolysis (3.3%). No treatment-related deaths occurred. Conclusions Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC. Randomized trials to evaluate this new combination strategy are warranted. Trial registration This trial was registered on July 27, 2018, at ClinicalTrials.gov (identifier: NCT03603756).

【 授权许可】

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