Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program.
Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program.
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DOI：
10.1186/s12885-016-2440-9
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发表时间：
2016-07-07
期刊：
影响因子：
3.8
通讯作者：
Andre T
中科院分区：
文献类型：
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作者：
Adenis A;de la Fouchardiere C;Paule B;Burtin P;Tougeron D;Wallet J;Dourthe LM;Etienne PL;Mineur L;Clisant S;Phelip JM;Kramar A;Andre T
随机试验表明，对于经过标准治疗后病情进展的转移性结直肠癌 (mCRC) 患者，瑞戈非尼比安慰剂具有生存获益。我们评估了在现实生活中接受瑞戈非尼治疗的患者的生存和安全性结果。 REBECCA 是一项同情使用计划的队列研究，旨在评估标准疗法难治性转移性结直肠癌患者的生存率、安全性和与瑞戈非尼相关的潜在预后因素。使用单变量和多变量 Cox 比例风险回归模型评估根据不同患者和肿瘤特征的治疗效果。在同情使用计划的 1178 名患者中，有 654 名患者属于完整分析组。中位随访时间为 16.5 个月。中位生存期为 5.6 个月。 12 个月的生存率为 22%。生存率受到以下变量的独立不利影响：体能状态差、从最初诊断转移到开始使用瑞戈非尼的时间短、初始瑞戈非尼剂量低、> 3 个转移部位、存在肝转移和 KRAS 突变。我们确定了死亡风险低、中、高的患者预后组，中位生存期分别为 9.2、5.2 和 2.5 个月。 524 名患者 (80%) 经历了至少一种与瑞戈非尼相关的不良事件，最常见的是疲劳、手足皮肤反应、腹泻、厌食、动脉高血压和粘膜炎。 REBECCA 中瑞戈非尼的安全性和有效性与随机试验中的相似。我们的预后模型确定了从瑞戈非尼中获得最小和最大益处的转移性结直肠癌患者亚组。临床试验.gov NCT02310477。
Randomized trials have shown a survival benefit for regorafenib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies. We evaluated survival and safety outcomes in patients treated with regorafenib in a real-life setting. REBECCA is a cohort study nested within a compassionate use program designed to evaluate survival, safety, and potential prognostic factors for outcome associated with regorafenib in patients with mCRC refractory to standard therapies. Treatment effects according to various patient and tumour characteristics were evaluated using univariate and multivariate Cox proportional hazards regression models. Of 1178 patients in the compassionate use program, 654 were in the full analysis set. Median follow-up was 16.5 months. Median survival was 5.6 months. The 12-month survival rate was 22 %. Survival was independently and unfavourably affected by the following variables: poor performance status, short time from initial diagnosis of metastases to the start of regorafenib, low initial regorafenib dose, >3 metastatic sites, presence of liver metastases, and KRAS mutations. We identified prognostic groups of patients with low, intermediate, and high risk of death, with a median survival of 9.2, 5.2, and 2.5 months, respectively. Five-hundred-twenty-four patients (80 %) experienced at least one regorafenib-related adverse event, most commonly, fatigue, hand-foot skin reaction, diarrhea, anorexia, arterial hypertension, and mucositis. The safety and efficacy profile of regorafenib in REBECCA are similar to those in randomized trials. Our prognostic model identified subgroups of mCRC patients who derived a minimal and maximum benefit from regorafenib. Clinicaltrials.gov NCT02310477.