Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, Australia.
Int J Clin Oncol. 2020 Sep;25(9):1672-1677. doi: 10.1007/s10147-020-01698-7. Epub 2020 May 16.
Sorafenib is a current first-line treatment option for advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the impact of early adverse events (AEs) requiring sorafenib dose adjustment on survival outcomes of patients with advanced HCC.
The study was a secondary analysis of the phase III clinical trial NCT00699374. A landmark Cox proportional hazard analysis was used to evaluate the association between early AEs requiring sorafenib dose adjustment with survival outcomes. The primary outcome was overall survival (OS) with progression-free survival (PFS) as secondary.
AEs requiring sorafenib dose adjustment within the first 28 days of therapy were significantly associated with OS (HR [95% CI]; dose interruption = 0.9 [0.7-1.2]; dose reduction = 0.6 [0.5-0.9]; discontinuation = 1.7 [0.9-3.4]; P = 0.005). No statistically significant association with PFS was identified (P = 0.148).
Sorafenib dose interruptions and reduction due to AEs did not compromise the survival outcomes of patient with advanced HCC. Patients who required a sorafenib dose reduction were observed to have more favourable OS compared to those who did not experience an AE which required a dose adjustment.
索拉非尼是目前治疗晚期肝细胞癌（HCC）的一线治疗选择。本研究旨在评估早期需要调整索拉非尼剂量的不良事件（AE）对晚期 HCC 患者生存结果的影响。
本研究是 III 期临床试验 NCT00699374 的二次分析。采用里程碑 Cox 比例风险分析评估治疗早期需要调整索拉非尼剂量的 AE 与生存结果之间的关联。主要结局是总生存期（OS），无进展生存期（PFS）为次要结局。
治疗的前 28 天内需要调整索拉非尼剂量的 AE 与 OS 显著相关（HR [95%CI]；剂量中断 = 0.9 [0.7-1.2]；剂量减少 = 0.6 [0.5-0.9]；停药 = 1.7 [0.9-3.4]；P = 0.005）。与 PFS 无统计学显著相关性（P = 0.148）。
AE 导致的索拉非尼剂量中断和减少并未影响晚期 HCC 患者的生存结果。与未经历需要剂量调整的 AE 的患者相比，需要索拉非尼剂量减少的患者的 OS 更有利。
