替氟尿苷替匹嘧啶与贝伐珠单抗治疗难治性转移性结直肠癌
Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.
机构信息
From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Université Paris Cité, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); Núcleo de Pesquisa e Ensino da Rede São Camilo, São Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
出版信息
N Engl J Med. 2023 May 4;388(18):1657-1667. doi: 10.1056/NEJMoa2214963.
BACKGROUND
In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.
METHODS
We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).
RESULTS
A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).
CONCLUSIONS
Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).
背景
在之前的一项 3 期临床试验中，接受曲氟尿苷替匹嘧啶（FTD-TPI）治疗的转移性结直肠癌患者的总生存期延长。来自单组和随机 2 期试验的初步数据表明，在贝伐珠单抗的基础上加用 FTD-TPI 有可能延长生存期。
方法
我们按 1:1 的比例随机分配既往接受不超过 2 种化疗方案治疗晚期结直肠癌的成年患者，分别接受 FTD-TPI 联合贝伐珠单抗（联合组）或 FTD-TPI 单药（FTD-TPI 组）治疗。主要终点是总生存期。次要终点是无进展生存期和安全性，包括从 ECOG 体力状态评分 0 或 1 恶化至 2 或更高（评分范围为 0 至 5，得分越高表示残疾程度越大）的时间。
结果
共有 246 例患者被分配至每组。联合组的中位总生存期为 10.8 个月，FTD-TPI 组为 7.5 个月（死亡风险比，0.61；95%置信区间[CI]，0.49 至 0.77；P<0.001）。联合组的中位无进展生存期为 5.6 个月，FTD-TPI 组为 2.4 个月（疾病进展或死亡的风险比，0.44；95%CI，0.36 至 0.54；P<0.001）。两组最常见的不良反应均为中性粒细胞减少症、恶心和贫血。均未报告与治疗相关的死亡。联合组 ECOG 体力状态评分从 0 或 1 恶化至 2 或更高的中位时间为 9.3 个月，FTD-TPI 组为 6.3 个月（风险比，0.54；95%CI，0.43 至 0.67）。
结论
在难治性转移性结直肠癌患者中，FTD-TPI 联合贝伐珠单抗治疗的总生存期长于 FTD-TPI 单药治疗。（由 Servier 和 Taiho Oncology 资助；SUNLIGHT ClinicalTrials.gov 编号，NCT04737187；EudraCT 编号，2020-001976-14。）
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