Xu Jianming, Xu Nong, Bai Yuxian, Liu Rongrui, Mao Chenyu, Sui Hong, Wang Xiaofei, Jiang Qian, Dou Yiwei
Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of Medical Oncology, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, China.
Oncoimmunology. 2020 Dec 31;10(1):1864908. doi: 10.1080/2162402X.2020.1864908.
Anti-PD-1 monoclonal antibody is approved as an option for third-line treatment of advanced gastric and gastroesophageal junction (G/GEJ) cancer in several countries, but no anti-PD-1 monoclonal antibody treatment is yet approved for first-line treatment of advanced G/GEJ cancer. We report a phase Ib trial of HX008, a highly selective, humanized anti-programmed death-1 monoclonal antibody, plus oxaliplatin and capecitabine as first-line treatment for advanced G/GEJ cancer. Patients with previously untreated, locally advanced or metastatic G/GEJ cancer were enrolled. All patients received HX008 3 mg/kg intravenously every 3 weeks, oxaliplatin 130 mg/m intravenously on day 1 every 3 weeks (up to 6 cycles), and capecitabine 1000 mg/m orally twice daily for 14 days continuous dosing followed by a 7-day break. The primary end point was the incidence of adverse events and serious adverse events. In total, 35 patients were enrolled. Median follow-up was 12.7 months. Most frequent (>10%) grade ≥3 treatment-related adverse events were anemia (27.5%), neutropenia (20%), thrombocytopenia (17.1%), leukopenia (17.1%) and fatigue (17.3%). Objective response rate was 60.0% (95% confidence interval [CI] 42.1-76.1%). Disease control rate was 77.1% (95% CI 59.9-89.6). Median time to response and duration of response were 1.4 months (range 1.3-2.9) and 12.3 months (range 1.4-17.9+), respectively. Median PFS was 9.2 months (95% CI 5.4-not reached). These results demonstrated that HX008 combined with oxaliplatin plus capecitabine was well tolerated and demonstrated encouraging efficacy as first-line treatment for advanced G/GEJ cancer. This study was registered in china, register number was CTR20181270.
抗程序性死亡蛋白1（PD-1）单克隆抗体在多个国家被批准作为晚期胃癌和胃食管交界（G/GEJ）癌三线治疗的一种选择，但尚无抗PD-1单克隆抗体治疗被批准用于晚期G/GEJ癌的一线治疗。我们报告了一项1b期试验，该试验使用高度选择性的人源化抗程序性死亡蛋白1单克隆抗体HX008联合奥沙利铂和卡培他滨作为晚期G/GEJ癌的一线治疗方案。招募了既往未接受过治疗、局部晚期或转移性G/GEJ癌患者。所有患者每3周静脉注射一次3mg/kg的HX008，每3周的第1天静脉注射130mg/m²的奥沙利铂（最多6个周期），卡培他滨1000mg/m²口服，每日2次，连续给药14天，随后休息7天。主要终点是不良事件和严重不良事件的发生率。总共招募了35名患者。中位随访时间为12.7个月。最常见的（>10%）≥3级治疗相关不良事件为贫血（27.5%）、中性粒细胞减少（20%）、血小板减少（17.1%）、白细胞减少（17.1%）和疲劳（17.3%）。客观缓解率为60.0%（95%置信区间[CI]42.1-76.1%）。疾病控制率为77.1%（95%CI59.9-89.6）。中位缓解时间和缓解持续时间分别为1.4个月（范围1.3-2.9）和12.3个月（范围1.4-17.9+）。中位无进展生存期为9.2个月（95%CI5.4-未达到）。这些结果表明，HX008联合奥沙利铂加卡培他滨耐受性良好，作为晚期G/GEJ癌的一线治疗显示出令人鼓舞的疗效。本研究在中国注册，注册号为CTR20181270。
