瑞戈非尼是一种口服多激酶抑制剂。CORRECT试验评估了瑞戈非尼在多线治疗后的转移性结直肠癌中的作用。纳入标准包括记录在案的转移性结直肠癌及在最后一种标准治疗中进展或治疗后3个月进展的转移性结直肠癌。所有病人随机以2:1入组接受最佳支持治疗联合瑞戈替尼（160mg od po，连续三周停一周）或联合安慰剂。主要终点是总生存期，次要终点包括无进展生存期，总有效率，疾病控制率，安全性及生活质量。应用单变量cox回归分析在预先设定的亚组中进行分析，以评估其疗效。结果发现：760个病人被随机分配（瑞戈替尼组505人，安慰剂组255人）。总生存期达符合预先设定的中期分析目标。瑞戈替尼组，其总生存期及无进展生存期显著高于安慰剂组（OS风险比 0.77，中位生存期6.4个月VS5个月，PFS风险比0.19，中位PFS1.9个月VS1.7个月）。在探索性亚组分析中，不同地区、不同年龄、到随机入组时的诊断时间，先前治疗方案数、K-RAS状态均观察到了OS和PFS的获益（见列表）。最常见的瑞戈替尼相关的3度以上不良反应包括：手足皮肤反应（16.6%），乏力，高血压，腹泻以及皮疹或脱屑。生活质量数据即将发布。结论：瑞戈替尼相对于安慰剂，表现出显著地提高多线治疗后转移性结直肠癌的OS和PFS，在亚组分析中也达到了获益水平。

Phase III CORRECT trial of regorafenib in metastatic colorectal cancer (mCRC).

Digestive Oncology Unit, Leuven Cancer Institute, University Hospital Gasthuisberg, Leuven, Belgium; Ospedale San Martino, Medical Oncology, Genova, Italy; Ospedale Niguarda Ca' Granda, Milan, Italy; University of Pisa, Pisa, Italy; CRLC Val d'Aurelle, Montpellier, France; Cliniques Universitaires Saint-Luc, UCL, Brussels, Belgium; University Hospital Robert Debre, Reims, France; Radiology and Oncology Centre, Institut Sainte-Catherine, Avignon, France; Catholic University of Sacred Heart, Rome, Italy; Centre Oscar Lambret, Lille, France; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; National Cancer Center Hospital East, Kashiwa, Japan; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Ohio State University Medical Center, Columbus, OH; Mayo Clinic, Rochester, MN; Bayer HealthCare Pharmaceuticals, Montville, NJ; Bayer HealthCare Pharmaceuticals, Berlin, Germany

Abstract Disclosures

3502

Background: Regorafenib (REG) is an oral multi-kinase inhibitor. The CORRECT trial was conducted to eva luate REG in patients (pts) with mCRC who had progressed after all approved standard therapies. Methods: Enrollment criteria included documented mCRC and progression during or 3 months after last standard therapy. Pts were randomized 2:1 to receive best supportive care plus either REG (160 mg od po, 3 wks on/1 wk off) or placebo (PL). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate, disease control rate, safety and quality of life (QoL). Efficacy analyses across prespecified subgroups were eva luated using univariate Cox regression. Results: 760 pts were randomized (REG: 505; PL: 255). The OS primary endpoint was met at a preplanned interim analysis. OS and PFS were significantly improved in REG arm compared to PL arm: hazard ratio (HR) for OS 0.77 (95% CI 0.64-0.94, 1-sided p=0.0052), median OS 6.4 vs 5.0 mos; HR for PFS 0.49 (95% CI 0.42-0.58, 1-sided p<0.000001), median PFS 1.9 vs 1.7 mos. Comparable OS and PFS benefits were observed in exploratory subgroup analyses by region, age, time from diagnosis of mCRC to randomization, prior lines of treatment, and KRAS status (shown in table). The most common grade 3+ AEs related to REG were hand-foot skin reaction (16.6%), fatigue (9.6%), hypertension (7.2%), diarrhea (7.2%) and rash/desquamation (5.8%). QoL data will be presented. Conclusions: REG demonstrated statistically significant improvement in OS and PFS over PL, as well as comparable efficacy benefits across pt subgroups analyzed.

Subgroups	N	OS		PFS
		HR	95% CI	HR	95% CI
Region*
North America, Western EU,  Israel and Australia	632	0.77	0.62-0.95	0.50	0.42-0.60
Asia	104	0.79	0.43-1.46	0.43	0.28-0.68
Age
< 65 yrs	475	0.72	0.56-0.91	0.42	0.34-0.51
65 yrs	285	0.86	0.61-1.19	0.65	0.50-0.86
Time from Dx of mCRC to randomization
< 18 mo	140	0.82	0.53-1.25	0.58	0.41-0.84
18 mo	620	0.76	0.61-0.95	0.48	0.40-0.58
No. of prior treatment lines on or after metastatic disease
3	395	0.79	0.60-1.04	0.53	0.43-0.67
> 3	365	0.75	0.56-0.99	0.47	0.37-0.59
KRAS^
WT	299	0.65	0.48-0.90	0.48	0.36-0.62
MUT	430	0.87	0.67-1.12	0.53	0.43-0.65