Trifluridine/Tipiracil (TAS‐102) in Refractory Metastatic Colorectal Cancer: A Multicenter Register in the Frame of the Italian Compassionate Use Program

Abstract

<p class="first" id="d904621e554">A new fluoropyrimidine recently entered the scene of metastatic colorectal cancer (mCRC): trifluridine/tipiracil, also known as TAS‐102. Improving the cost/efficacy ratio of TAS‐102 in mCRC is needed to avoid toxicities in a definitely palliative setting. ECOG performance score, LDH levels, and time from diagnosis of metastatic disease may help identify patients most likely to benefit. Properly designed prognostic tools, such as the "ColonLife" nomogram, may allow for better treatment decisions for patients with limited life expectancy. </p><div class="section"> <a class="named-anchor" id="onco12453-sec-0001"> <!-- named anchor --> </a> <h5 class="section-title" id="d904621e560">Background.</h5> <p id="d904621e562">TAS‐102 is indicated for patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, available therapies. Given the complete inefficacy in half of patients, the lack of predictive factors, the palliative setting, and the financial and clinical toxicity, optimizing the cost‐benefit ratio is crucial. The “ColonLife” nomogram allows an estimate of the 12‐week life expectancy of patients with refractory mCRC. </p> </div><div class="section"> <a class="named-anchor" id="onco12453-sec-0002"> <!-- named anchor --> </a> <h5 class="section-title" id="d904621e565">Materials and Methods.</h5> <p id="d904621e567">We collected data from patients treated at eight Italian centers in the compassionate use program. Baseline characteristics of patients who were or were not progression free at 6 months were compared. The discriminative ability of the ColonLife nomogram was assessed. Among patients who received both TAS‐102 and regorafenib, clinical outcomes of the two sequences were compared. </p> </div><div class="section"> <a class="named-anchor" id="onco12453-sec-0003"> <!-- named anchor --> </a> <h5 class="section-title" id="d904621e570">Results.</h5> <p id="d904621e572">This study included 341 patients. Six (2%) and 93 (27%) patients achieved response and disease stabilization, respectively. The median progression‐free survival (PFS) was 2.4 months with an estimated 6‐month PFS rate of 19%; the median overall survival (OS) was 6.2 months. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, normal lactate dehydrogenase (LDH), and a time from the diagnosis of metastatic disease of &gt;18 months were independently associated with higher chances of a patient being progression free at 6 months. The discriminative ability of ColonLife was confirmed. Among 121 patients who received both regorafenib and TAS‐102, no differences in first or second PFS or OS were reported between the two sequences. </p> </div><div class="section"> <a class="named-anchor" id="onco12453-sec-0004"> <!-- named anchor --> </a> <h5 class="section-title" id="d904621e575">Conclusion.</h5> <p id="d904621e577">One out of five patients achieves clinical benefit with TAS‐102. ECOG PS, LDH, and time from diagnosis of metastatic disease may help to identify these patients. Excluding patients with very short life expectancy appears a reasonable approach. </p> </div><div class="section"> <a class="named-anchor" id="onco12453-sec-1005"> <!-- named anchor --> </a> <h5 class="section-title" id="d904621e580">Implications for Practice.</h5> <p id="d904621e582">Improving the cost‐efficacy ratio of TAS‐102 in metastatic colorectal cancer is needed to spare useless toxicities in a definitely palliative setting. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, and time from the diagnosis of metastatic disease may help to identify patients more likely to achieve benefit. Properly designed prognostic tools (i.e., the “ColonLife” nomogram) may enable excluding from further treatments patients with very limited life expectancy. </p> </div><p class="first" id="d904621e586">摘要</p><p id="d904621e588"> <b> <i>背景。</i> </b>TAS‐102 适用于先前接受过现有疗法治疗或者被认定无法接受现有疗法治疗的转移性结直肠癌(mCRC)患者。由于对半数患者完全无效,缺乏预测因素,采取姑息治疗以及经济因素和临床毒性因素,因此,优化成本效益比显得至关重要。“ColonLife”列线图可以估算出难治性mCRC患者的预期寿命为 12 周。 </p><p id="d904621e596"> <b> <i>材料和方法。</i> </b>我们收集了在8家参与同情使用计划的意大利中心接受治疗的患者的数据,并在 6 个月时对病情有进展与病情无进展的患者的基本特征进行了比较。我们还对 ColonLife 列线图的鉴别能力进行了评估。在同时服用 TAS‐102 和瑞格非尼的患者中,我们对两种服药顺序的临床效果进行了比较。 </p><p id="d904621e604"> <b> <i>结果。</i> </b>本研究入组341名患者。其中分别有6名患者(2%)和93名患者(27%)的病情缓解及疾病稳定。中位无进展生存期(PFS)为2.4个月,估算的6个月PFS率为19%;中位总生存期(OS)为6.2个月。东部肿瘤协作组体能状态(ECOG PS)评分为0,乳酸脱氢酶(LDH)正常,诊断转移的时间超过18个月,均与患者在6个月时无疾病进展独立相关。ColonLife的鉴别能力得到了证实。在服用瑞格非尼和TAS‐102的121名患者中,未收到两种服药顺序在PFS或OS存在差异的报告。 </p><p id="d904621e612"> <b> <i>结论。</i> </b>五分之一的患者在服用TAS‐102后得到临床受益。ECOG PS、LDH和诊断转移的时间可帮助确定这些患者。排除预期寿命很短的患者似乎是一种合理的方法。 </p><p id="d904621e620">实践意义</p><p id="d904621e622">需要提高TAS‐102在治疗转移性结直肠癌过程中的成本疗效比率,进而消除其在明确姑息治疗环境中的无用毒性。东部肿瘤协作组体能状态评分、乳酸脱氢酶水平以及诊断转移的时间可帮助确定更有可能获得疗效的患者。设计合理的预后工具(如“ColonLife”列线图)可排除预期寿命非常有限的患者去接受进一步的治疗。</p>