Stivarga是安全的，改善了不可切除的肝细胞癌患者的总生存期

StephenW

Nault JC. Lancet. 2017;doi:10.1016/S0140-6736(16)32480-1.
January 23, 2017

Stivarga was safe and improved overall survival for patients with unresectable hepatocellular carcinoma, according to data from the RESORCE clinical trial recently published in The Lancet.

“The global incidence of liver cancer continues to increase and has more than tripled in the United States over the last three decades, and currently there are no proven or approved systemic second-line treatment options for patients with advanced HCC,” Jordi Bruix, MD, head of the Barcelona Liver Clinic Group, Hospital Clinic, University of Barcelona, Spain, and trial investigator, said in a press release. “The improvement in overall survival seen with [Stivarga] in the RESORCE study signals the addition of a potential option in this treatment setting.”
Jordi Bruix, MD

Jordi Bruix

Bruix and colleagues randomly assigned 573 patients with unresectable HCC whose disease progressed after treatment with Nexavar (sorafenib, Bayer HealthCare) to treatment with either 160 mg of Stivarga (regorafenib, Bayer; n = 379) for 3 weeks on and 1 week off, or placebo (n = 194) with 28 days constituting one full treatment cycle.

Results showed patients treated with regorafenib had a longer median overall survival (OS) of 10.6 months compared with 7.8 months for patients treated with placebo plus best supportive care (HR = 0.62; 95% CI, 0.5-0.78). The median progression-free survival was 3.1 months in the regorafenib-treated group compared with 1.5 months in the control group (HR = 0.46; 95% CI, 0.37‒0.56).

Disease control rate defined by mRECIST criteria was 65.2% in regorafenib-treated patients compared with the placebo group (36.1%; P < .001). The overall response rate (complete and partial) was 10.6% vs. 4.1% (P = .005).

More patients in the regorafenib-treated group experienced grade 3 adverse events (79.7%) compared with placebo (58.5%). Common grade 3 adverse events included hypertension, hand-foot skin reaction, fatigue and diarrhea. Approximately 68% of patients treated with regorafenib underwent dose modification due to adverse events compared with 31.1% of patients treated with placebo.

Patients treated with placebo had a higher mortality rate compared with regorafenib-treated patients after 30 days post-treatment (19.7% vs. 13.4%).

Bayer submitted data from the RESORCE study for marketing authorization of regorafenib for the treatment of unresectable HCC in the U.S. and worldwide in November 2016.

The researchers concluded: “Regorafenib significantly improved OS in patients with HCC who progressed during treatment with sorafenib. Adverse events were consistent with the known safety profile of regorafenib.”

“This study represents a breakthrough in the management of hepatocellular carcinoma, since it provides evidence for clinical benefits in an area that was an unmet medical need,” Josep M. Llovet, MD, founder and director of the Liver Cancer Program and professor of medicine and Liver Diseases at the Icahn School of Medicine at Mount Sinai, said in a press release. “Regorafenib has shown it can improve survival in patients with advanced hepatocellular carcinoma progressing on sorafenib. Previously, no treatment was available for these patients.”

In light of these results, “it is clear that regorafenib will become the standard of care as a second-line treatment following sorafenib failure in patients with advanced HCC,” Jean-Charles Nault, MD, PhD, of the French Institute of Health and Medical Research, wrote in a related editorial. However, “the main area of uncertainty lies in the tolerance and efficacy of regorafenib in patients not tolerating sorafenib,” he noted. “Further data are warranted in this subpopulation of patients.” – by Melinda Stevens and Adam Leitenberger

Reference:

Bruix J, et al. Abstract #LBA-03. Presented at: European Society of Medical Oncology World Congress on Gastrointestinal Cancer; June 29-July 2, 2016; Barcelona, Spain.

Disclosure: This study was funded by Bayer. Bruix reports consulting for AbbVie, Arqule, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, BTG, Gilead Sciences, Kowa, Novartis, Onxeo, OSI, Roche and Terumo. Nault reports no relevant financial disclosures.

Editor's note: These data were originally presented at the European Society of Medical Oncology 18th World Congress on Gastrointestinal Cancer. This article was updated on January 23 with additional information after publication in The Lancet.

StephenW

Nault JC。柳叶刀。 2017年; doi：10.1016 / S0140-6736（16）32480-1。
2017年1月23日

根据最近发表在The Lancet的RESORCE临床试验的数据，Stivarga是安全的，改善了不可切除的肝细胞癌患者的总生存期。

“过去三十年间，全球肝癌发病率继续增加，在美国增加了三倍以上，目前还没有针对晚期肝癌患者的行之有效的系统性二线治疗方案”，Jordi Bruix，MD ，西班牙巴塞罗那大学巴塞罗那肝脏诊所组长，医院诊所，和试验研究者，在一份新闻稿中说。 “在RESORCE研究中，[Stivarga]观察到的总生存期的改善表明在这种治疗设置中增加了潜在的选择。
Jordi Bruix，MD

Jordi Bruix

Bruix及其同事随机分配了573例不可切除的HCC，其患者在用Nexavar（索拉非尼，Bayer HealthCare）治疗后，用160mg Stivarga（regorafenib，Bayer; n = 379）治疗3周和1周，安慰剂（n = 194）与28天编码一个完整的治疗周期。

结果显示，使用regorafenib治疗的患者的中位总生存期（OS）为10.6个月，而使用安慰剂+最佳支持治疗的患者为7.8个月（HR = 0.62; 95％CI，0.5-0.78）。 regorafenib治疗组的中位无进展生存期为3.1个月，而对照组为1.5个月（HR = 0.46; 95％CI，0.37-0.56）。

在用regorafenib治疗的患者中，与安慰剂组相比，mRECIST标准定义的疾病控制率为65.2％（36.1％; P <0.001）。总体反应率（完全和部分）为10.6％对4.1％（P = 005）。

治疗的患者与安慰剂（58.5％）相比经历3级不良事件（79.7％）。常见的3级不良事件包括高血压，手足皮肤反应，疲劳和腹泻。大约68％的用Regorafenib治疗的患者由于不良事件而进行剂量调整，而用安慰剂治疗的患者为31.1％。

用安慰剂治疗的患者在治疗30天后与regorafenib治疗的患者相比具有更高的死亡率（19.7％对13.4％）。

Bayer提交了来自RESORCE研究的数据，用于在2016年11月在美国和全世界治疗不可切除的HCC的regorafenib的市场授权。

医生总结道：“Regorafenib显着改善了索拉菲尼治疗期间进展的HCC患者的OS。不良事件与regorafenib的已知安全性一致。

“这项研究代表了肝细胞癌的管理的突破，因为它提供了在一个未满足的医疗需求的领域的临床益处的证据，”肝癌计划的创始人和主任，医学教授和西奈山伊坎医学院的肝病，在一份新闻稿中说。 “Regorafenib已经表明，它可以提高索拉非尼治疗晚期肝细胞癌患者的生存率。以前，没有治疗这些患者。

根据这些结果，“显然，regorafenib将成为在晚期HCC患者中索拉菲尼失败后作为二线治疗的标准治疗”，法国健康研究所的Jean-Charles Nault博士，然而，“不确定性的主要领域在于regorafenib在不耐受索拉非尼的患者中的耐受性和功效，”他指出。 “在这个亚群患者中进一步的数据是有保证的。 - 由Melinda Stevens和Adam Leitenberger

参考：

Brux J，et al。摘要＃LBA-03。介绍：欧洲肿瘤学会世界胃肠癌大会; 2016年6月29日 - 7月2日;西班牙巴塞罗那。

披露：本研究由拜耳资助。 Bruix向AbbVie，Arqule，Bayer，Boehringer Ingelheim，Bristol-Myers Squibb，BTG，Gilead Sciences，Kowa，Novartis，Onxeo，OSI，Roche和Terumo提供咨询。 。

编者按：这些数据最初是在欧洲肿瘤医学学会第十八届世界胃肠道癌大会上提出的。这篇文章于1月23日更新，并在“柳叶刀”上发表后提供了更多信息。