a Clinical Pharmacology Unit , Zealand University Hospital , Roskilde , Denmark.
b Department of Oncology , Herlev University Hospital , Herlev , Denmark.
Acta Oncol. 2019 Aug;58(8):1149-1157. doi: 10.1080/0284186X.2019.1605192. Epub 2019 Apr 19.
The treatment options for patients with therapy refractory metastatic colorectal cancer (mCRC) are sparse. TAS-102 (FTD/TPI) is a new oral anti-tumour agent composed of a nucleoside analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil, indicated for patients with mCRC who are refractory to standard therapies. This study summarizes published and unpublished experience with FTD/TPI in clinical practice settings. The Medline/PubMed, Embase and Cochrane Library databases were searched to identify observational studies on FTD/TPI monotherapy for mCRC. Papers describing use of FTD/TPI monotherapy outside clinical trials in series of patients evaluable for effectiveness were eligible. The outcomes of interest were median progression free survival (mPFS), median overall survival (mOS) as well as mean PFS time restricted to six months (PFS) and mean OS time restricted to one year (OS). Results of the pooled analyses of observational studies were compared to the results of the Japanese phase II trial and the two phase III trials, RECOURSE and TERRA. Seven published and two unpublished studies with 1008 patients from 64 centres were included for analysis. The pooled mPFS was 2.2 months (95% CI 2.1 to 2.3 months), and the pooled mOS was 6.6 months (95% CI 6.1 to 7.1 months). PFS was 2.9 months (95% CI 2.6 to 3.1 months) and OS was 6.8 (95% CI 6.0 to 7.5) months. While these results all reflect RECOURSE, the pooled mOS is lower than in the phase II trial and the OS is inferior to both the phase II trial and TERRA. This systematic review and a meta-analysis indicates that in real life settings, the survival benefit of FTD/TPI monotherapy in patients with therapy refractory mCRC reflects the outcomes in RECOURSE but is inferior to outcomes in the two Asian efficacy trials. What is already known TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). A Japanese phase II trial and two phase III trials, RECOURSE and TERRA, demonstrated that FTD/TPI prolonged overall survival. What this study adds This systematic review and meta-analysis of real life data from 64 sites indicates that the effectiveness in daily clinical practice settings of FTD/TPI monotherapy in late stage mCRC reflects the outcomes in RECOURCE but is inferior to the outcomes in the Japanese phase II trial and TERRA.
治疗难治性转移性结直肠癌（mCRC）患者的选择方案有限。TAS-102（FTD/TPI）是一种新型口服抗肿瘤药物，由核苷类似物三氟胸苷（FTD）和胸苷磷酸化酶抑制剂替匹嘧啶（TPI）组成，适用于对标准治疗耐药的 mCRC 患者。本研究总结了 FTD/TPI 在临床实践中的应用经验。检索了 Medline/PubMed、Embase 和 Cochrane 图书馆数据库，以确定关于 FTD/TPI 单药治疗 mCRC 的观察性研究。符合条件的是描述在临床试验之外，在可评估疗效的患者系列中使用 FTD/TPI 单药治疗的研究。研究的主要终点为无进展生存期（PFS）、总生存期（OS），次要终点为 PFS 时间受限至 6 个月（PFS）和 OS 时间受限至 1 年（OS）。对观察性研究的汇总分析结果与日本 II 期试验和两项 III 期试验 RECURSE 和 TERRA 的结果进行了比较。对 64 个中心的 1008 名患者进行了 7 项已发表和 2 项未发表的研究分析。汇总的中位无进展生存期（mPFS）为 2.2 个月（95%CI 2.1 至 2.3 个月），中位总生存期（mOS）为 6.6 个月（95%CI 6.1 至 7.1 个月）。PFS 为 2.9 个月（95%CI 2.6 至 3.1 个月），OS 为 6.8 个月（95%CI 6.0 至 7.5 个月）。虽然这些结果都反映了 RECURSE 的情况，但汇总的 mOS 低于 II 期试验，OS 也低于 II 期试验和 TERRA。这项系统评价和荟萃分析表明，在真实环境中，TAS-102（Lonsurf）在治疗难治性 mCRC 患者中的单药治疗的生存获益反映了 RECURSE 的结果，但劣于两项亚洲疗效试验的结果。已知的内容 TAS 102（Lonsurf）是一种三氟胸苷（FTD）和替匹嘧啶（TPI）的口服固定剂量复方制剂，适用于治疗耐药转移性结直肠癌（mCRC）患者的三线治疗。一项日本 II 期试验和两项 III 期试验 RECURSE 和 TERRA 表明，FTD/TPI 延长了总生存期。本研究增加的内容这项对来自 64 个地点的真实数据的系统评价和荟萃分析表明，FTD/TPI 单药治疗晚期 mCRC 在日常临床实践中的有效性反映了 RECOURCE 的结果，但劣于日本 II 期试验和 TERRA 的结果。
