纳武利尤单抗联合伊匹单抗二线治疗食管鳞癌老年患者（RAMONA）：一项多中心、开放标签的 2 期试验。
Second-line therapy with nivolumab plus ipilimumab for older patients with oesophageal squamous cell cancer (RAMONA): a multicentre, open-label phase 2 trial.
机构信息
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
出版信息
Lancet Healthy Longev. 2022 Jun;3(6):e417-e427. doi: 10.1016/S2666-7568(22)00116-7. Epub 2022 Jun 9.
BACKGROUND
The overall survival of patients with advanced and refractory oesophageal squamous cell carcinoma, mostly aged 65 years and older, is poor. Treatment with PD-1 antibodies showed improved progression-free survival and overall survival. We assessed the safety and efficacy of combined nivolumab and ipilimumab therapy in this population.
METHODS
This multicentre, open-label, phase 2 trial done in 32 sites in Germany included patients aged 65 years and older with oesophageal squamous cell carcinoma and disease progression or recurrence following first-line therapy. Patients were treated with nivolumab (240 mg fixed dose once every 2 weeks, intravenously) in the safety run-in phase and continued with nivolumab and ipilimumab (nivolumab 240 mg fixed dose once every 2 weeks and ipilimumab 1 mg/kg once every 6 weeks, intravenously). The primary endpoint was overall survival, which was compared with a historical cohort receiving standard chemotherapy in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03416244.
FINDINGS
Between March 2, 2018, and Aug 20, 2020, we screened 75 patients with advanced oesophageal squamous cell carcinoma. We enrolled 66 patients (50 [76%] men and 16 [24%] women; median age 70·5 years [IQR 67·0-76·0]), 44 (67%) of whom received combined nivolumab and ipilimumab therapy and 22 (33%) received nivolumab alone. Median overall survival time at the prespecified data cutoff was 7·2 months (95% CI 5·7-12·4) and significantly higher than in a historical cohort receiving standard chemotherapy (p=0·0063). The most common treatment-related adverse events were fatigue (12 [29%] of 42), nausea (11 [26%]), and diarrhoea (ten [24%]). Grade 3-5 treatment-related adverse events occurred in 13 (20%) of 66 patients. Treatment-related death occurred in one patient with bronchiolitis obliterans while on nivolumab and ipilimumab treatment.
INTERPRETATION
Patients aged at least 65 years, with advanced oesophageal squamous cell carcinoma might benefit from combined nivolumab and ipilimumab therapy in second-line treatment.
FUNDING
Bristol Myers Squibb.
背景
大多数年龄在 65 岁及以上的晚期和难治性食管鳞状细胞癌患者的总体生存率较差。PD-1 抗体的治疗显示出改善的无进展生存期和总生存期。我们评估了该人群中纳武利尤单抗联合伊匹单抗治疗的安全性和疗效。
方法
这项多中心、开放标签、2 期试验在德国的 32 个地点进行，纳入了年龄在 65 岁及以上的患有食管鳞状细胞癌且在一线治疗后疾病进展或复发的患者。在安全性预试验阶段，患者接受纳武利尤单抗（每 2 周静脉注射 240mg 固定剂量）治疗，然后继续接受纳武利尤单抗和伊匹单抗（每 2 周静脉注射 240mg 固定剂量，每 6 周静脉注射 1mg/kg 伊匹单抗）治疗。主要终点是总体生存期，在意向治疗人群中与接受标准化疗的历史队列进行比较。这项研究在 ClinicalTrials.gov 注册，NCT03416244。
结果
2018 年 3 月 2 日至 2020 年 8 月 20 日，我们筛选了 75 例晚期食管鳞状细胞癌患者。我们纳入了 66 例患者（50 例[76%]为男性，16 例[24%]为女性；中位年龄 70.5 岁[IQR 67.0-76.0]），其中 44 例（67%）接受了纳武利尤单抗联合伊匹单抗治疗，22 例（33%）接受了纳武利尤单抗单药治疗。在预设数据截止时的中位总生存期为 7.2 个月（95%CI 5.7-12.4），明显高于接受标准化疗的历史队列（p=0.0063）。最常见的与治疗相关的不良事件是疲劳（42 例中有 12 例[29%]）、恶心（11 例[26%]）和腹泻（10 例[24%]）。66 例患者中有 13 例（20%）发生 3-5 级与治疗相关的不良事件。1 例患者在接受纳武利尤单抗和伊匹单抗治疗时发生细支气管炎性闭塞。
解释
年龄至少为 65 岁、患有晚期食管鳞状细胞癌的患者可能从二线治疗中的纳武利尤单抗联合伊匹单抗治疗中获益。
资金来源
百时美施贵宝公司。
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