Ogasawara Sadahisa, Chiba Tetsuhiro, Ooka Yoshihiko, Suzuki Eiichiro, Kanogawa Naoya, Saito Tomoko, Motoyama Tenyu, Tawada Akinobu, Kanai Fumihiko, Yokosuka Osamu
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Invest New Drugs. 2016 Apr;34(2):255-60. doi: 10.1007/s10637-016-0323-1. Epub 2016 Jan 14.
Since the approval of sorafenib, no other agent has been proven to show survival benefits in clinical trials involving patients with advanced hepatocellular carcinoma (HCC) resistant to sorafenib. Prognostic factors for survival after tumor progression in sorafenib-treated patients are critical for designing second-line trials.
To determine the factors affecting the post-progression survival (PPS) after sorafenib treatment, additional analyses were conducted using fixed data obtained from our previous prospective study. Data on patients with advanced HCC treated with sorafenib were analyzed in view of patient characteristics at the time of tumor progression and the progression pattern (intra-/extrahepatic growth or emergence of new intra-/extrahepatic lesions).
Of the 89 enrolled patients, 70 were diagnosed with disease progression according to the Response Evaluation Criteria in Solid Tumors version 1.1. Multivariate Cox's regression analysis revealed that Child-Pugh scores of ≥7, macrovascular invasion (MVI), and alpha-fetoprotein of >400 ng/mL were independent predictors of poor PPS. Although both extrahepatic metastasis (EHM) and MVI were characteristics of advanced HCC, EHM was not determined as a prognostic factor. Additionally, the emergence of new extrahepatic lesions also served as an independent indicator of a poor prognosis. The PPS of the patients was well stratified according to the index based on the sum of these prognostic factors, ranging from 0 to 4.
Child-Pugh score of ≥7, AFP of >400 ng/mL, MVI, and new extrahepatic lesions at the time of progression may be utilized to assess the prognosis and taken into consideration when designing second-line trials.
自索拉非尼获批以来，在涉及对索拉非尼耐药的晚期肝细胞癌（HCC）患者的临床试验中，尚无其他药物被证明具有生存获益。索拉非尼治疗患者肿瘤进展后的生存预后因素对于设计二线试验至关重要。
为了确定影响索拉非尼治疗后进展后生存（PPS）的因素，我们使用先前前瞻性研究获得的固定数据进行了额外分析。根据肿瘤进展时的患者特征和进展模式（肝内/肝外生长或新的肝内/肝外病变出现），对接受索拉非尼治疗的晚期HCC患者的数据进行了分析。
在89名入组患者中，根据实体瘤疗效评价标准1.1版，70名被诊断为疾病进展。多因素Cox回归分析显示，Child-Pugh评分≥7、大血管侵犯（MVI）和甲胎蛋白>400 ng/mL是PPS不良的独立预测因素。尽管肝外转移（EHM）和MVI都是晚期HCC的特征，但EHM未被确定为预后因素。此外，新的肝外病变出现也是预后不良的独立指标。根据基于这些预后因素总和的指数（范围为0至），患者的PPS得到了很好的分层。
Child-Pugh评分≥7、进展时甲胎蛋白>400 ng/mL、MVI和新的肝外病变可用于评估预后，并在设计二线试验时予以考虑。 4
