Regorafenib versus Cabozantinib as a Second-Line Treatment for Advanced Hepatocellular Carcinoma: An Anchored Matching-Adjusted Indirect Comparison of Efficacy and Safety.

IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver Cancer Pub Date : 2023-06-01 DOI:10.1159/000527403
Philippe Merle, Masatoshi Kudo, Stanimira Krotneva, Kirhan Ozgurdal, Yun Su, Irina Proskorovsky
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引用次数: 2

Abstract

Introduction: The tyrosine kinase inhibitors regorafenib and cabozantinib remain the mainstay in second-line treatment of advanced hepatocellular carcinoma (HCC). There is currently no clear evidence of superiority in efficacy or safety to guide choice between the two treatments.

Methods: We conducted an anchored matching-adjusted indirect comparison using individual patient data from the RESORCE trial of regorafenib and published aggregate data from the CELESTIAL trial of cabozantinib. Second-line HCC patients with prior sorafenib exposure of ≥3 months were included in the analyses. Hazard ratios (HRs) and restricted mean survival time (RMST) were estimated to quantify differences in overall survival (OS) and progression-free survival (PFS). Safety outcomes compared were rates of grade 3 or 4 adverse events (AEs), occurring in >10% of patients, and discontinuation or dose reduction due to treatment-related AEs.

Results: After matching adjustment for differences in baseline patient characteristics, regorafenib showed a favorable OS (HR, 0.80; 95% CI: 0.54, 1.20) and ∼3-month-longer RMST over cabozantinib (RMST difference, 2.76 months; 95% CI: -1.03, 6.54), although not statistically significant. For PFS, there was no numerical difference in HR (HR, 1.00; 95% CI: 0.68, 1.49) and no clinically meaningful difference based on RMST analyses (RMST difference, -0.59 months; 95% CI: -1.83, 0.65). Regorafenib showed a significantly lower incidence of discontinuation (risk difference, -9.2%; 95% CI: -17.7%, -0.6%) and dose reductions (-15.2%; 95% CI: -29.0%, -1.5%) due to treatment-related AEs (any grade). Regorafenib was also associated with a lower incidence (not statistically significant) of grade 3 or 4 diarrhea (risk difference, -7.1%; 95% CI: -14.7%, 0.4%) and fatigue (-6.3%; 95% CI: -14.6%, 2.0%).

Conclusion: This indirect treatment comparison suggests, relative to cabozantinib, that regorafenib could be associated with favorable OS (not statistically significant), lower rates of dose reductions and discontinuation due to treatment-related AEs, and lower rates of severe diarrhea and fatigue.

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瑞非尼与卡博赞替尼作为晚期肝细胞癌的二线治疗:锚定匹配调整后的疗效和安全性的间接比较
简介:酪氨酸激酶抑制剂瑞戈非尼和卡博赞替尼仍然是晚期肝细胞癌(HCC)二线治疗的主要药物。目前还没有明确的证据表明这两种治疗方法在疗效或安全性上有优势。方法:我们使用来自reorafenib的resce试验的个体患者数据和来自cabozantinib的CELESTIAL试验的汇总数据进行了锚定匹配调整的间接比较。先前索拉非尼暴露≥3个月的二线HCC患者被纳入分析。评估风险比(hr)和限制平均生存时间(RMST)以量化总生存期(OS)和无进展生存期(PFS)的差异。比较的安全性结果是3级或4级不良事件(ae)的发生率,发生在>10%的患者中,以及由于治疗相关的ae而停药或减少剂量。结果:在对基线患者特征差异进行匹配调整后,瑞非尼显示出良好的OS (HR, 0.80;95% CI: 0.54, 1.20)和比卡博赞替尼更长3个月的RMST (RMST差异,2.76个月;95% CI: -1.03, 6.54),但无统计学意义。对于PFS, HR没有数值差异(HR, 1.00;95% CI: 0.68, 1.49),基于RMST分析无临床意义差异(RMST差异,-0.59个月;95% ci: -1.83, 0.65)。瑞非尼的停药发生率显著降低(风险差-9.2%;95% CI: -17.7%, -0.6%)和剂量减少(-15.2%;95% CI: -29.0%, -1.5%),原因是与治疗相关的ae(任何级别)。瑞非尼还与3级或4级腹泻发生率较低相关(无统计学意义)(风险差异为-7.1%;95% CI: -14.7%, 0.4%)和疲劳(-6.3%;95% ci: -14.6%, 2.0%)。结论:这一间接治疗比较表明,相对于卡博赞替尼,瑞戈非尼可能与良好的OS(无统计学意义)、较低的剂量减少率和因治疗相关不良反应而停药率以及较低的严重腹泻和疲劳率相关。
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来源期刊
Liver Cancer
Liver Cancer Medicine-Oncology
CiteScore
20.80
自引率
7.20%
发文量
53
审稿时长
16 weeks
期刊介绍: Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.
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