Riaño Ioana, Martín Leticia, Varela Maria, Serrano Trinidad, Núñez Oscar, Mínguez Beatriz, Rodrigues Pedro M, Perugorria Maria J, Banales Jesus M, Arenas Juan I
Department of Liver and Gastrointestinal Diseases, Clinical Research Unit, Donostia University Hospital-Biodonostia Health Research Institute, 20014 San Sebastian, Spain.
Digestive Service, Hepatology Unit, Asturias Central University Hospital, The University Institute of Oncology of Asturias (IUOPA), FINBA, 33006 Oviedo, Spain.
Cancers (Basel). 2020 Jul 14;12(7):1900. doi: 10.3390/cancers12071900.
Pravastatin has demonstrated anti-tumor activity in preclinical and clinical studies. This multicentric randomized double-blind placebo-controlled phase II study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination on the overall survival (OS) and time to progression (TTP) of patients with advanced hepatocellular carcinoma (aHCC). A total of 31 patients were randomized. Median OS did not differ between both groups (12.4 months for the sorafenib + pravastatin group vs. 11.6 months for the control group). Of note, however, the radiological TTP was higher in patients treated with sorafenib + pravastatin than in the control group (9.9 months vs. 3.2 months; = 0.008). Considering all the study population, the presence of portal vein thrombosis (PVT) was associated with worse OS, being lower in patients with PVT compared to patients without PVT (6.3 months vs. 14.8 months; = 0.026). Data also showed a decrease in OS in patients with vascular invasion (VI) compared to patients who did not present it (6.3 months vs. 14.8 months; = 0.041). The group of patients without dermatological events (DE) showed lower OS (6.9 months vs. 14.5 months; = 0.049). In conclusion, combination of sorafenib + pravastatin was safe and well-tolerated, prolonging the TTP of patients with aHCC but not improving the OS compared to sorafenib + placebo. The absence of PVT and VI and the development of DE are positive prognostic factors of sorafenib response.
普伐他汀在临床前和临床研究中已显示出抗肿瘤活性。这项多中心随机双盲安慰剂对照II期研究（NCT01418729）调查了索拉非尼+普伐他汀联合用药对晚期肝细胞癌（aHCC）患者总生存期（OS）和疾病进展时间（TTP）的疗效和安全性。共有31例患者被随机分组。两组的中位OS无差异（索拉非尼+普伐他汀组为12.4个月，对照组为11.6个月）。然而，值得注意的是，接受索拉非尼+普伐他汀治疗的患者的放射学TTP高于对照组（9.9个月对3.2个月；P = 0.008）。在所有研究人群中，门静脉血栓形成（PVT）的存在与较差的OS相关，有PVT的患者的OS低于无PVT的患者（6.3个月对14.8个月；P = 0.026）。数据还显示，有血管侵犯（VI）的患者的OS低于无血管侵犯的患者（6.3个月对14.8个月；P = 0.041）。无皮肤事件（DE）的患者组的OS较低（6.9个月对14.5个月；P = 0.049）。总之，索拉非尼+普伐他汀联合用药安全且耐受性良好，可延长aHCC患者的TTP，但与索拉非尼+安慰剂相比未改善OS。无PVT和VI以及出现DE是索拉非尼反应的阳性预后因素。
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