Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Groupement Hospitalier Lyon Nord, Hepatology Unit, Lyon, France.
J Hepatol. 2018 Aug;69(2):353-358. doi: 10.1016/j.jhep.2018.04.010. Epub 2018 Apr 26.
BACKGROUND & AIMS: The RESORCE trial showed that regorafenib improves overall survival (OS) in patients with hepatocellular carcinoma progressing during sorafenib treatment (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.50-0.78; p <0.0001). This exploratory analysis describes outcomes of sequential treatment with sorafenib followed by regorafenib.
In RESORCE, 573 patients were randomized 2:1 to regorafenib 160 mg/day or placebo for 3 weeks on/1 week off. Efficacy and safety were evaluated by last sorafenib dose. The time from the start of sorafenib to death was assessed. Time to progression (TTP) in RESORCE was analyzed by TTP during prior sorafenib treatment.
HRs (regorafenib/placebo) for OS by last sorafenib dose were similar (0.67 for 800 mg/day; 0.68 for <800 mg/day). Rates of grade 3, 4, and 5 adverse events with regorafenib by last sorafenib dose (800 mg/day vs. <800 mg/day) were 52%, 11%, and 15% vs. 60%, 10%, and 12%, respectively. Median times (95% CI) from the start of sorafenib to death were 26.0 months (22.6-28.1) for regorafenib and 19.2 months (16.3-22.8) for placebo. Median time from the start of sorafenib to progression on sorafenib was 7.2 months for the regorafenib arm and 7.1 months for the placebo arm. An analysis of TTP in RESORCE in subgroups defined by TTP during prior sorafenib in quartiles (Q) showed HRs (regorafenib/placebo; 95% CI) of 0.66 (0.45-0.96; Q1); 0.26 (0.17-0.40; Q2); 0.40 (0.27-0.60; Q3); and 0.54 (0.36-0.81; Q4).
These exploratory analyses show that regorafenib conferred a clinical benefit regardless of the last sorafenib dose or TTP on prior sorafenib. Rates of adverse events were generally similar regardless of the last sorafenib dose.
This analysis examined characteristics and outcomes of patients with hepatocellular carcinoma who were treated with regorafenib after they had disease progression during sorafenib treatment. Regorafenib provided clinical benefit to patients regardless of the pace of their disease progression during prior sorafenib treatment and regardless of their last sorafenib dose. The sequence of sorafenib followed by regorafenib for hepatocellular carcinoma may extend survival beyond what has been previously reported. ClinicalTrials.gov NCT01774344.
RESORCE 试验表明，regorafenib 可改善索拉非尼治疗期间进展的肝细胞癌患者的总生存期（HR 0.62，95%CI 0.50-0.78；p<0.0001）。本探索性分析描述了索拉非尼序贯治疗后再使用regorafenib 的结果。
在 RESORCE 试验中，573 例患者按 2:1 的比例随机分配至regorafenib 160mg/天或安慰剂治疗，每 3 周给药 1 次，停药 1 周。疗效和安全性评估的截止时间为最后一次索拉非尼剂量。从开始索拉非尼治疗到死亡的时间进行评估。RESORCE 中的无进展生存期（TTP）通过先前索拉非尼治疗期间的 TTP 进行分析。
根据最后一次索拉非尼剂量，OS 的 HR（regorafenib/安慰剂）相似（800mg/天为 0.67；<800mg/天为 0.68）。最后一次索拉非尼剂量（800mg/天 vs. <800mg/天）时，regorafenib 的 3/4/5 级不良事件发生率分别为 52%、11%和 15%，安慰剂分别为 60%、10%和 12%。从开始索拉非尼治疗到死亡的中位时间（95%CI）分别为索拉非尼治疗的regorafenib 组 26.0 个月（22.6-28.1）和安慰剂组 19.2 个月（16.3-22.8）。从开始索拉非尼治疗到索拉非尼治疗进展的中位时间分别为regorafenib 组 7.2 个月和安慰剂组 7.1 个月。根据 TTP 在先前索拉非尼治疗的四分位数（Q）中的分组，对 RESORCE 中的 TTP 进行分析，显示 HR（regorafenib/安慰剂；95%CI）为 0.66（0.45-0.96；Q1）；0.26（0.17-0.40；Q2）；0.40（0.27-0.60；Q3）和 0.54（0.36-0.81；Q4）。
这些探索性分析表明，regorafenib 提供了临床获益，无论最后一次索拉非尼剂量或先前索拉非尼治疗中的 TTP 如何。不良事件的发生率通常与最后一次索拉非尼剂量无关。
本分析检查了在索拉非尼治疗期间疾病进展后接受regorafenib 治疗的肝细胞癌患者的特征和结局。无论先前索拉非尼治疗中疾病进展的速度如何，也无论最后一次索拉非尼剂量如何，regorafenib 均为患者提供了临床获益。索拉非尼序贯 regorafenib 治疗肝细胞癌可能会延长生存期，超过之前的报道。ClinicalTrials.gov NCT01774344。
