Yoshino Takayuki, Taieb Julien, Kuboki Yasutoshi, Pfeiffer Per, Kumar Amit, Hochster Howard S
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Hôpital Européen Georges-Pompidou, Université Paris-Cité, SIRIC CARPEM, Paris, France.
Ther Adv Med Oncol. 2023 Jan 21;15:17588359221146137. doi: 10.1177/17588359221146137. eCollection 2023.
Trifluridine/tipiracil plus bevacizumab (FTD/TPI + BEV) has shown efficacy and tolerability in refractory metastatic colorectal cancer (mCRC). Because randomized controlled trial (RCT) data comparing FTD/TPI + BEV with FTD/TPI are lacking, this meta-analysis evaluated outcomes with both regimens.
Electronic databases, congress proceedings (past 3 years), trial registries, systematic review bibliographies, gray literature, and guidelines through June 2021 were searched for RCTs, non-RCTs, and prospective observational studies involving >20 previously treated patients with mCRC receiving FTD/TPI + BEV or FTD/TPI. Absolute and relative disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse event (AE) rates, and discontinuation rates due to AEs were evaluated using fixed-effects and random-effects models. Study quality, heterogeneity, and publication bias were assessed.
In all, 29 of 875 screened publications were selected (26 studies: 5 RCTs, 11 non-RCTs, and 10 prospective observational studies). One RCT compared FTD/TPI + BEV with FTD/TPI. FTD/TPI + BEV FTD/TPI had a higher absolute DCR [64% (6 studies; = 289) 43% (10 studies; = 2809)], median PFS [4.2 (5 studies; = 244) 2.6 (6 studies; = 1781) months], 12-month PFS [9% (5 studies; = 244) 3% (6 studies; = 1781)], median OS [9.8 (5 studies; = 244) 8.1 (6 studies; = 1814) months], and 12-month OS [38% (5 studies; = 244) 32% (6 studies; = 1814)]. Grade ⩾3 febrile neutropenia, asthenia/fatigue, diarrhea, nausea, and vomiting rates were similar (1%-7%). Grade ⩾3 neutropenia rate was higher with FTD/TPI + BEV than with FTD/TPI [43% (6 studies; = 294) 29% (12 studies; = 7139)]. Discontinuation rates due to AEs were similar [8% (5 studies; = 244) and 7% (10 studies; = 3724)]. Low study quality, heterogeneity, and/or publication bias were detected in certain instances.
Despite fewer patients treated with the combination, this meta-analysis consistently suggested that FTD/TPI + BEV provides benefits over FTD/TPI in refractory mCRC and has similar safety, except for more frequent grade ⩾3 neutropenia.
曲氟尿苷/替匹嘧啶联合贝伐珠单抗（FTD/TPI + BEV）已在难治性转移性结直肠癌（mCRC）中显示出疗效和耐受性。由于缺乏比较FTD/TPI + BEV与FTD/TPI的随机对照试验（RCT）数据，本荟萃分析评估了两种治疗方案的结局。
检索截至2021年6月的电子数据库、会议论文集（过去3年）、试验注册库、系统评价参考文献、灰色文献和指南，以查找涉及20例以上既往接受治疗的mCRC患者接受FTD/TPI + BEV或FTD/TPI的RCT、非RCT和前瞻性观察性研究。使用固定效应和随机效应模型评估绝对和相对疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）、不良事件（AE）发生率以及因AE导致的停药率。评估研究质量、异质性和发表偏倚。
总共从875篇筛选的出版物中选择了29篇（26项研究：5项RCT、11项非RCT和10项前瞻性观察性研究）。一项RCT比较了FTD/TPI + BEV与FTD/TPI。FTD/TPI + BEV的绝对DCR更高[64%（6项研究；n = 289）对43%（10项研究；n = 2809）]，中位PFS[4.2个月（5项研究；n = 244）对2.6个月（6项研究；n = 1781）]，12个月PFS[9%（5项研究；n = 244）对3%（6项研究；n = 1781）]，中位OS[9.8个月（5项研究；n = 244）对8.1个月（6项研究；n = 1814）]，以及12个月OS[38%（5项研究；n = 244）对32%（6项研究；n = 1814）]。≥3级发热性中性粒细胞减少、乏力/疲劳、腹泻、恶心和呕吐发生率相似（1%-7%）。FTD/TPI + BEV的≥3级中性粒细胞减少发生率高于FTD/TPI[43%（6项研究；n = 294）对29%（12项研究；n = 7139）]。因AE导致的停药率相似[8%（5项研究；n = 244）和7%（10项研究；n = 3724）]。在某些情况下检测到研究质量低、异质性和/或发表偏倚。
尽管接受联合治疗的患者较少，但本荟萃分析一致表明，在难治性mCRC中，FTD/TPI + BEV比FTD/TPI更具优势，且安全性相似，只是≥3级中性粒细胞减少更频繁。
