Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, Australia.
Mechanisms in Cell Biology and Disease Research Group, Clinical and Health Sciences, Cancer Research Institute, University of South Australia, Adelaide, Australia.
J Cancer Res Clin Oncol. 2020 Oct;146(10):2693-2697. doi: 10.1007/s00432-020-03261-3. Epub 2020 May 24.
Sorafenib is an oral tyrosine kinase inhibitor (TKI) and first-line treatment option for advanced hepatocellular carcinoma (HCC). Preliminary evidence indicates proton pump inhibitors (PPI) may affect the absorption of TKIs through decreased gut dissolution. This study aims to evaluate the impact of PPI use on the survival outcomes of advanced HCC patients treated with sorafenib.
The study was a secondary analysis of individual-participant data from the phase III clinical trial NCT00699374. Cox proportional hazard analysis was used to evaluate the association between baseline PPI use and survival outcomes. Overall survival (OS) was the primary outcome with progression-free survival (PFS) secondary.
In a cohort of 542 advanced HCC patients initiating sorafenib treatment, 122 were concomitantly using a PPI at baseline. No significant associations between baseline PPI use and OS were identified on univariable (HR [95% CI]; 1.01 [0.80-1.28], P = 0.93) and adjusted (1.10 [0.82-1.41], P = 0.62) analysis. Furthermore, no significant associations between baseline PPI use and PFS were identified on univariable (0.96 [0.76-1.21], P = 0.73) and adjusted (1.11 [0.86-1.44], P = 0.41) analysis.
In a large high-quality dataset, PPI use was not observed to compromise the survival outcomes of advanced HCC patients initiated on sorafenib.
索拉非尼是一种口服酪氨酸激酶抑制剂（TKI），也是晚期肝细胞癌（HCC）的一线治疗选择。初步证据表明质子泵抑制剂（PPI）可能通过降低肠道溶解来影响 TKI 的吸收。本研究旨在评估 PPI 使用对接受索拉非尼治疗的晚期 HCC 患者生存结果的影响。
该研究是对 III 期临床试验 NCT00699374 的个体参与者数据的二次分析。Cox 比例风险分析用于评估基线 PPI 使用与生存结果之间的关联。总生存期（OS）是主要终点，无进展生存期（PFS）是次要终点。
在开始接受索拉非尼治疗的 542 例晚期 HCC 患者队列中，122 例患者在基线时同时使用 PPI。在单变量（HR [95%CI]；1.01 [0.80-1.28]，P = 0.93）和调整（1.10 [0.82-1.41]，P = 0.62）分析中，基线时使用 PPI 与 OS 之间均无显著关联。此外，在单变量（0.96 [0.76-1.21]，P = 0.73）和调整（1.11 [0.86-1.44]，P = 0.41）分析中，基线时使用 PPI 与 PFS 之间也无显著关联。
在一个大型高质量数据集，PPI 使用并未观察到影响接受索拉非尼治疗的晚期 HCC 患者的生存结果。
