Background: 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.
Materials and methods: 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.
Results: 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).
Conclusion: 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.
Implications for practice: 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.
摘要
背景.本研究比较瑞戈非尼与曲氟尿苷/Tipiracil（TFTD）治疗接受标准化疗无效的转移性结直肠癌（mCRC）患者的疗效, 尽管这两种药物已经获批准用于临床用途, 但尚不清楚应将哪种药物用于初始治疗。
材料与方法.从日本的24家机构回顾性地收集了2014年6月至2015年9月间接受瑞戈非尼或TFTD治疗的mCRC患者和未接受药物治疗患者的临床数据。对倾向评分进行基线特征校正, 使用Cox比例风险模型, 评价总生存期（OS）。
结果.共550例患者（瑞戈非尼组223例, TFTD组327例）满足所有标准。瑞戈非尼组与TFTD组的中位OS分别为7.9个月[95%置信区间（CI）为6.8‐9.2]和7.4个月（95% CI, 6.6‐8.3）。校正后的倾向评分分析表明, 两组间的OS相似[校正后的风险比（HR）为0.96, 95% CI, 0.78–1.18]。在亚组分析中观察到与年龄间有显著相互作用。瑞戈非尼显示在年龄<65岁患者中的生存率更高（HR, 1.29；95%CI, 0.98–1.69）, 而TFTD显示年龄≥65岁患者中的生存率更高（HR, 0.78；95%CI, 0.59–1.03）。
结论.瑞戈非尼组与TFTD组mCRC患者间的OS没有显著差异。按年龄选择药物可能影响生存率, 在将来的研究中应确定区分这两种药物的明确预测性生物标志物。
对临床实践的启示：关于接受标准化疗无效的转移性结直肠癌患者的既往研究证实, 与安慰剂相比, 瑞戈非尼和曲氟尿苷/Tipiracil均可提高总生存率, 但尚未开展头对头试验。本项大型、多中心、观察性研究回顾性地比较了瑞戈非尼与曲氟尿苷/Tipiracil治疗550例接受标准化疗无效的转移性结直肠癌（mCRC）患者的疗效, 这些患者均可以获得这两种药物。虽然在校正倾向评分的分析中未发现这两种药物的总生存率存在差异, 但亚组分析中瑞戈非尼组显示年龄<65岁的患者的生存率更高, 而曲氟尿苷/Tipiracil组显示年龄≥65岁的患者的生存率更高。
Keywords: Colorectal cancer; Propensity score; Regorafenib; TAS‐102; Trifluridine/tipiracil.
© 2017 The Authors The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.