Abstract：
BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated.
METHODS: PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses.
RESULTS: Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses.
CONCLUSIONS: Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.
METHODS: PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses.
RESULTS: Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses.
CONCLUSIONS: Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.
摘要：
背景：二线以外的转移性结直肠癌（mCRC）的最佳治疗仍存在疑问。除了护理剂的标准(regorafenib，REG,或氟尿苷/替哌嘧啶，FTD/TPI),化疗再激发或再引入（CTr/r）是临床实践中通常考虑的，尽管证据薄弱。CTr/r的预后表现，在此评估此设置中的REG和FTD/TPI。
方法：PROSERpYNa是一个多中心，观察,回顾性研究,其中难治性mCRC患者，在至少2行CT后进展，用CTr/r治疗，REG或FTD/TPI,被认为是合格的，并被纳入2个独立的数据集（探索性和有效性）。主要终点是总生存期（OS）；次要终点是研究者评估的无进展生存期（PFS），客观反应率（RR）和安全性。对生存分析进行倾向评分调整。
结果：收集了来自3个意大利机构的1月10日至1月19日之间接受治疗的患者的数据（探索性和验证性数据集分别为341和181种治疗）。在探索性队列中，中位操作系统（18.5与6.5个月)，PFS（6.1vs.3.5个月）和RR（28.6%与1.4%)与REG/FTD/TPI相比，CTr/r明显更长。在倾向评分分析中保留了生存获益，校正了多变量分析中确定的独立预后因素。此外，这些结果在验证队列分析中得到证实.
结论：虽然回顾性的方式，CTr/r在现实世界中被证明是一个有价值的选择，与标准治疗药物相比，以中等毒性为代价提供更好的结果。
方法：PROSERpYNa是一个多中心，观察,回顾性研究,其中难治性mCRC患者，在至少2行CT后进展，用CTr/r治疗，REG或FTD/TPI,被认为是合格的，并被纳入2个独立的数据集（探索性和有效性）。主要终点是总生存期（OS）；次要终点是研究者评估的无进展生存期（PFS），客观反应率（RR）和安全性。对生存分析进行倾向评分调整。
结果：收集了来自3个意大利机构的1月10日至1月19日之间接受治疗的患者的数据（探索性和验证性数据集分别为341和181种治疗）。在探索性队列中，中位操作系统（18.5与6.5个月)，PFS（6.1vs.3.5个月）和RR（28.6%与1.4%)与REG/FTD/TPI相比，CTr/r明显更长。在倾向评分分析中保留了生存获益，校正了多变量分析中确定的独立预后因素。此外，这些结果在验证队列分析中得到证实.
结论：虽然回顾性的方式，CTr/r在现实世界中被证明是一个有价值的选择，与标准治疗药物相比，以中等毒性为代价提供更好的结果。
