Background: Regorafenib is a recognised treatment for refractory metastatic colorectal cancer (mCRC). The phase II ReDOS trial indicated that a stepwise dose escalation approach could enhance tolerability and persistence while maintaining efficacy. The ReTrITA study, a significant multicentre real-world cohort in Italy, served as the foundation for this sub-analysis concentrating solely on patients treated with regorafenib. Methods: This retrospective analysis encompassed 713 patients treated at 17 Italian centres from 2012 to 2023. Patients were categorised into two groups: ReDOS-like escalation (n= 313) and fixed dosing (no-ReDOS) (n= 400). The endpoints assessed were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and safety. Survival was assessed using Kaplan–Meier and Cox models, accompanied by exploratory subgroup analyses. Results: The median overall survival (OS) was comparable between the escalation and fixed dosing groups, recorded at 7.4 months and 6.7 months, respectively (HR 1.00, 95% CI 0.85–1.18,p= 0.93). Progression-free survival (PFS) demonstrated a significant improvement with escalation, recording 3.1 months compared to 3.9 months (HR 0.76, 95% CI 0.65–0.89,p= 0.0007). Subgroup analyses demonstrated a consistent progression-free survival (PFS) benefit in patients aged ≥70 years (HR 0.71,p= 0.015), with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1 (HR 0.76,p= 0.022), RAS wild-type tumours (HR 0.69,p= 0.026), and rectal primaries (HR 0.72,p= 0.043). The disease control rate (DCR) and objective response rate (ORR) were comparable, at 23.2% versus 25.3% and 2.0% compared 2.6%, respectively. Although not statistically significant, the fixed dose group’s duration of response (DoR) was numerically longer (15.4 months) than that of the variable dosing group (8.9 months). A lower percentage of patients experienced grade 3/4 adverse events with escalation (35.4% compared to 39.5%,p= 0.0042). Conclusions: This sub-analysis of the ReTrITA cohort demonstrates that regorafenib dose escalation is achievable in real-world settings, resulting in notable improvements in progression-free survival and enhanced tolerability, while not adversely affecting overall survival. These results support and improve the findings of the ReDOS study, showing that dosage escalation is possible and helpful in a diverse, unselected group of people, which is what is performed in routine oncology treatment. The findings are consistent with both randomised and observational studies, endorsing individualised dosing as a practical strategy in refractory mCRC.
背景：瑞戈非尼是公认的难治性转移性结直肠癌（mCRC）治疗药物。II期ReDOS试验表明，阶梯式剂量递增方法可在保持疗效的同时提高耐受性和治疗持续性。ReTrITA研究作为意大利一项重要的多中心真实世界队列研究，为本项亚组分析提供了基础，该分析专门聚焦于接受瑞戈非尼治疗的患者群体。 方法：本回顾性分析纳入2012年至2023年间意大利17个中心收治的713例患者。患者被分为两组：ReDOS式剂量递增组（n=313）和固定剂量组（非ReDOS组，n=400）。评估的终点包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DoR）以及安全性。生存分析采用Kaplan-Meier法和Cox模型，并辅以探索性亚组分析。 结果：剂量递增组与固定剂量组的中位总生存期（OS）相当，分别为7.4个月和6.7个月（HR 1.00，95% CI 0.85–1.18，p=0.93）。无进展生存期（PFS）在剂量递增组显著改善，为3.9个月，而固定剂量组为3.1个月（HR 0.76，95% CI 0.65–0.89，p=0.0007）。亚组分析显示，在年龄≥70岁（HR 0.71，p=0.015）、美国东部肿瘤协作组体能状态（ECOG PS）为0-1分（HR 0.76，p=0.022）、RAS野生型肿瘤（HR 0.69，p=0.026）以及原发灶位于直肠（HR 0.72，p=0.043）的患者中，无进展生存期（PFS）获益保持一致。疾病控制率（DCR）和客观缓解率（ORR）两组相当，分别为23.2%对25.3%和2.0%对2.6%。尽管无统计学显著性，固定剂量组的缓解持续时间（DoR）在数值上长于剂量递增组（15.4个月对8.9个月）。剂量递增组发生3/4级不良事件的患者比例较低（35.4%对39.5%，p=0.0042）。 结论：本项对ReTrITA队列的亚组分析表明，瑞戈非尼剂量递增在真实世界临床实践中是可行的，可显著改善无进展生存期并提高耐受性，且不影响总生存期。这些结果支持并拓展了ReDOS研究的发现，表明剂量递增在多样化、未经筛选的常规肿瘤治疗人群中是可行且有益的。该发现与随机研究和观察性研究结果一致，支持个体化剂量策略作为难治性mCRC的实用治疗选择。
肿瘤(癌症)患者之家