Shigesawa Taku, Suda Goki, Kimura Megumi, Shimazaki Tomoe, Maehara Osamu, Yamada Ren, Kitagataya Takashi, Suzuki Kazuharu, Nakamura Akihisa, Ohara Masatsugu, Umemura Machiko, Kawagishi Naoki, Nakai Masato, Sho Takuya, Natsuizaka Mitsuteru, Morikawa Kenichi, Ogawa Koji, Sakamoto Naoya
Department of Gastroenterology and Department of Hepatology, Graduate School of Medicine Hokkaido University Sapporo Japan.
JGH Open. 2020 Apr 11;4(5):880-888. doi: 10.1002/jgh3.12339. eCollection 2020 Oct.
Sorafenib and lenvatinib are first-line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear.
We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2-3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long-SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated.
Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib.
This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.
索拉非尼和乐伐替尼是不可切除肝细胞癌（HCC）的一线全身治疗药物。然而，它们的选择标准仍不明确。
我们纳入了2009年8月至2019年1月在北海道大学医院接受索拉非尼或乐伐替尼治疗的不可切除HCC患者。纳入持续治疗>2个月、每2 - 3个月接受计算机断层扫描评估且有完整临床数据的患者。乐伐替尼的反应者为有客观反应（OR）的患者，索拉非尼的反应者为疾病稳定（SD）超过6个月（长SD）或有OR的患者。评估了包括成纤维细胞生长因子（FGF）19和21、血管生成素2（ANG2）、肝细胞生长因子和血管内皮生长因子在内的治疗反应预测因素。
总体上，分别有27例和29例接受乐伐替尼和索拉非尼治疗的患者被纳入。乐伐替尼和索拉非尼的反应者分别为63%（17/27）和38%（11/29）。在接受索拉非尼治疗的患者中未发现显著的治疗反应预测因素。然而，基线血清FGF19和ANG2水平与乐伐替尼的治疗反应显著相关。所有接受乐伐替尼治疗且基线ANG2和FGF19水平低的患者（9/9）均获得OR。相反，基线ANG2和FGF19水平高的患者OR较低（13%；1/9）。接受索拉非尼治疗且基线ANG2和FGF19水平高的患者反应率为40%（2/5）。
据我们所知，本研究首次表明基线ANG2和FGF19水平可能有助于为不可切除HCC患者选择最佳的全身治疗。
