Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Oncologist. 2018 Jan;23(1):7-15. doi: 10.1634/theoncologist.2017-0275. Epub 2017 Sep 11.
This study compared the efficacy of regorafenib and trifluridine/tipiracil (TFTD) in patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy, because despite their clinical approval, it still remains unclear which of these two drugs should be used as initial treatment.
The clinical data of patients with mCRC who were treated with regorafenib or TFTD and those of drug-naive patients, between June 2014 and September 2015, were retrospectively collected from 24 institutions in Japan. Overall survival (OS) was evaluated using the Cox's proportional hazard models based on propensity score adjustment for baseline characteristics.
A total of 550 patients (223 patients in the regorafenib group and 327 patients in the TFTD group) met all criteria. The median OS was 7.9 months (95% confidence interval [CI], 6.8-9.2) in the regorafenib group and 7.4 months (95% CI, 6.6-8.3) in the TFTD group. The propensity score adjusted analysis showed that OS was similar between the two groups (adjusted hazard ratio [HR], 0.96; 95% CI, 0.78-1.18). In the subgroup analysis, a significant interaction with age was observed. Regorafenib showed favorable survival in patients aged <65 years (HR, 1.29; 95% CI, 0.98-1.69), whereas TFTD was favored in patients aged ≥65 years (HR, 0.78; 95% CI, 0.59-1.03).
No significant difference in OS between regorafenib and TFTD was observed in patients with mCRC. Although the choice of the drug by age might affect survival, a clearly predictive biomarker to distinguish the two drugs should be identified in further studies.
Previous studies of patients with metastatic colorectal cancer refractory to standard chemotherapy had demonstrated that both regorafenib and trifluridine/tipiracil could result in increased overall survival compared with placebo, but there are no head-to-head trials. This large, multicenter, observational study retrospectively compared the efficacy of regorafenib and trifluridine/tipiracil in 550 patients with metastatic colorectal cancer refractory to standard chemotherapy who had access to both drugs. Although no difference in overall survival was found between the two drugs in adjusted analysis using propensity score, regorafenib showed favorable survival in patients aged <65 years, whereas trifluridine/tipiracil was favored in patients aged ≥65 years in the subgroup analysis.
本研究比较了regorafenib 和 trifluridine/tipiracil（TFTD）在标准化疗耐药的转移性结直肠癌（mCRC）患者中的疗效，因为尽管这两种药物已获得临床批准，但仍不清楚哪种药物应作为初始治疗药物。
从日本 24 家机构回顾性收集了 2014 年 6 月至 2015 年 9 月接受regorafenib 或 TFTD 治疗的 mCRC 患者和初治患者的临床数据。使用基于倾向评分调整基线特征的 Cox 比例风险模型评估总生存期（OS）。
共有 550 名患者（regorafenib 组 223 名，TFTD 组 327 名）符合所有标准。regorafenib 组的中位 OS 为 7.9 个月（95%置信区间[CI]，6.8-9.2），TFTD 组为 7.4 个月（95%CI，6.6-8.3）。倾向评分调整分析显示，两组间 OS 无显著差异（调整后的风险比[HR]，0.96；95%CI，0.78-1.18）。亚组分析显示，年龄存在显著交互作用。regorafenib 在<65 岁患者中具有较好的生存获益（HR，1.29；95%CI，0.98-1.69），而 TFTD 在≥65 岁患者中更具优势（HR，0.78；95%CI，0.59-1.03）。
在标准化疗耐药的 mCRC 患者中，regorafenib 和 TFTD 的 OS 无显著差异。虽然按年龄选择药物可能会影响生存，但应在进一步的研究中确定明确的预测生物标志物来区分这两种药物。
先前对标准化疗耐药的转移性结直肠癌患者的研究表明，与安慰剂相比，regorafenib 和 trifluridine/tipiracil 均可使总生存期延长，但尚无头对头的试验。本项大型、多中心、观察性研究回顾性比较了 550 例标准化疗耐药的转移性结直肠癌患者接受 regorafenib 和 trifluridine/tipiracil 治疗的疗效，这些患者均有机会使用这两种药物。尽管在使用倾向评分进行调整分析时，两种药物在总生存期方面无差异，但亚组分析显示，regorafenib 在<65 岁患者中具有较好的生存获益，而 TFTD 在≥65 岁患者中更具优势。
