■一些研究表明,在难治性转移性结直肠癌(mCRC)中,氟尿苷/替吡嘧啶(TAS-102)加贝伐单抗(BEV)的疗效优于TAS-102的单一疗法。然而,目前尚不清楚中国人口是否可以从这种组合中受益。因此,我们进行了这项回顾性队列研究,以比较TAS-102联合BEV与TAS-102单药治疗难治性mCRC的疗效和安全性.
■这项回顾性队列研究纳入了湖南省肿瘤医院难治性mCRC患者(任何年龄)。主要纳入标准是组织病理学和/或影像学证实的难治性mCRC,世界卫生组织(WHO)的表现状态为0至2,器官功能充足,以及在2020年11月至2022年10月期间有或没有BEV的TAS-102的初始治疗。以前使用氟喹替尼或瑞戈非尼的治疗是允许的,但不是强制性的。适当收集基线人口统计学和临床特征。每2或3个治疗周期,通过计算机断层扫描(CT)扫描和临床评估对患者进行评估,直至疾病进展或失去随访.美国国家癌症研究所常见不良事件术语标准5.0(NCI-CTCAE5.0)表示为n(%)。主要终点是研究者评估的总生存期(OS)。由于这是一项回顾性队列研究,未进行样本量计算。将尽可能多地招募符合条件的患者。
■共纳入90名患者,包括58例接受TAS-102加BEV治疗的患者和另外32例接受TAS-102单药治疗的患者.已知的基线特征具有可比性(P<0.05)。中位随访时间为4.60个月(范围,0.20-22.80),TAS-102加BEV组的中位OS(mOS)时间长于TAS-102单药治疗组(10.83vs.7.43个月),但差异无统计学意义(P=0.79)。两组的中位无进展生存期(mPFS)时间具有可比性(4.67vs.4.30个月,P=0.96)。多因素Cox回归分析表明,在TAS-102后接受治疗或不使用BEV是OS的独立危险因素[风险比(HR)=0.25;95%置信区间(CI):0.09-0.71,P<0.01]。和先前使用西妥昔单抗治疗是PFS的独立保护因素(HR=0.17;95%CI:0.03-0.91,P=0.04)。在接受评估的70名患者中,与接受TAS-102单药治疗的患者相比,接受TAS-102+BEV的患者显示出更高的客观缓解率(ORR)和疾病控制率(DCR)的趋势(分别为P=0.16和P=0.29).两组不良事件(AE)相似,除了TAS-102+BEV组血小板计数下降(≥3级)的发生率显著较高.
■在OS和DCR方面,有一种趋势是支持BEV加TAS-102的组合,没有达到统计意义,这意味着在疗效方面没有明显的优势。进一步的前瞻性研究仍需得出明确的结论。
UNASSIGNED: Several studies demonstrated trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) had better efficacy than the monotherapy of TAS-102 in refractory metastatic colorectal cancer (mCRC). However, it remains unclear whether Chinese population can benefit from this combination or not. Hence, we conducted this retrospective cohort study to compare the efficacy and safety between TAS-102 plus BEV with TAS-102 monotherapy in refractory mCRC.
UNASSIGNED: This retrospective cohort study enrolled patients (any age) with refractory mCRC from Hunan Cancer Hospital. The main inclusion criteria were histopathologically and/or radiographically confirmed refractory mCRC, World Health Organization (WHO) performance status of 0 to 2, adequate organ function, and initial treatment of TAS-102 with or without BEV between November 2020 and October 2022. Previous therapy with fruquintinib or regorafenib was allowed but not mandatory. Baseline demographic and clinical characteristics were collected appropriately. Every 2 or 3 treatment cycles, the patients were assessed by computed tomography (CT) scans and clinical assessments until disease progression or loss to follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI-CTCAE 5.0) were presented as n (%). The primary endpoint was investigator-evaluated overall survival (OS). As this is a retrospective cohort study, sample size calculation was not performed. Eligible patients would be enrolled as many as possible.
UNASSIGNED: A total of 90 patients were enrolled, including 58 patients who received TAS-102 plus BEV and another 32 patients who received TAS-102 monotherapy. The known baseline characteristics were comparable (P<0.05). With a median follow-up of 4.60 months (range, 0.20-22.80), the median OS (mOS) time in the TAS-102 plus BEV group was longer than that in the TAS-102 monotherapy group (10.83 vs. 7.43 months), but the difference was not significant (P=0.79). The median progression-free survival (mPFS) time was comparable between the two groups (4.67 vs. 4.30 months, P=0.96). Multivariate Cox regression analysis demonstrated that undergoing therapy after TAS-102 either with or without BEV was an independent risk factor for OS [hazard ratio (HR) =0.25; 95% confidence interval (CI): 0.09-0.71, P<0.01], and previous treatment with cetuximab was an independent protective factor for PFS (HR =0.17; 95% CI: 0.03-0.91, P=0.04). Of the 70 patients who were evaluated, those receiving TAS-102 plus BEV showed trend of a higher objective response rate (ORR) and disease control rate (DCR) than those who received TAS-102 monotherapy (P=0.16 and P=0.29, respectively). Adverse events (AEs) were similar between the two groups, except that the incidence of platelet count decrease (grade ≥3) was significantly higher in the TAS-102 plus BEV group.
UNASSIGNED: There was a trend in favor of the combination of BEV plus TAS-102 regarding OS and DCR, without reaching statistical significance, and it means that there was no clear advantage of one over the other in terms of efficacy. Further prospective studies are still necessary to draw a definite conclusion.