Yen Clarence, Sharma Rohini, Rimassa Lorenza, Arizumi Tadaaki, Bettinger Dominik, Choo Huay Yee, Pressiani Tiziana, Burlone Michela E, Pirisi Mario, Giordano Laura, Abdulrahman Anisa, Kudo Masatoshi, Thimme Robert, Park Joong Won, Pinato David James
Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
Medical Oncology and Haematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan, Italy.
Liver Cancer. 2017 Nov;6(4):313-324. doi: 10.1159/000480441. Epub 2017 Sep 16.
Level I evidence supports the use of sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma, where heterogeneity in efficacy exists due to varying clinicopathologic features of the disease.
We evaluated whether prior treatment with curative or locoregional therapies influences sorafenib-specific survival.
From a prospective data set of 785 consecutive patients from international specialist centres, 264 patients (34%) were treatment naïve (TN) and 521 (66%) were pre-treated (PT), most frequently with transarterial chemoembolization ( = 413; 79%). The primary endpoint was overall survival (OS) from sorafenib initiation with prognostic factors tested on uni- and multivariate analyses.
Median OS for the entire cohort was 9 months; the median sorafenib duration was 2.8 months, with discontinuation being secondary to progression ( = 454; 58%) or toxicity ( = 149; 19%). PT patients had significantly longer OS than TN patients (10.5 vs. 6.6 months; < 0.001). Compared to TN patients, PT patients had a better Child-Pugh (CP) class (CP A: 57 vs. 47%; < 0.001) and a lower BCLC stage (BCLC A-B, 40 vs. 30%; = 0.007). PT status preserved an independent prognostic role ( = 0.002) following adjustment for BCLC stage, α-fetoprotein, CP class, aetiology, and post-sorafenib treatment status. PT patients were more likely to receive further anticancer treatment after sorafenib (31 vs. 9%; < 0.001).
Patients receiving sorafenib after having failed curative or locoregional therapies survive longer and are more likely to receive further treatment after sorafenib. This suggests an incremental benefit to OS from sequential exposure to multiple lines of therapy, justifying treatment stage migration in eligible patients.
一级证据支持索拉非尼用于巴塞罗那临床肝癌（BCLC）C期肝细胞癌患者，由于该疾病临床病理特征各异，其疗效存在异质性。
我们评估了先前接受根治性或局部区域治疗是否会影响索拉非尼特异性生存期。
从国际专科中心连续纳入的785例患者的前瞻性数据集中，264例患者（34%）未接受过治疗（TN），521例患者（66%）接受过预处理（PT），最常见的是经动脉化疗栓塞（n = 413；79%）。主要终点是从开始使用索拉非尼后的总生存期（OS），并在单因素和多因素分析中对预后因素进行检测。
整个队列的中位OS为9个月；索拉非尼的中位使用时长为2.8个月，停药主要是由于疾病进展（n = 454；58%）或毒性反应（n = 149；19%）。PT患者的OS明显长于TN患者（10.5个月对6.6个月；P < 0.001）。与TN患者相比，PT患者的Child-Pugh（CP）分级更好（CP A级：57%对47%；P < 0.001），BCLC分期更低（BCLC A - B期，40%对30%；P = 0.007）。在对BCLC分期、甲胎蛋白、CP分级、病因以及索拉非尼治疗后状态进行校正后，PT状态保留了独立的预后作用（P = 0.002）。PT患者在索拉非尼治疗后更有可能接受进一步的抗癌治疗（31%对9%；P < 0.001）。
在根治性或局部区域治疗失败后接受索拉非尼治疗的患者生存期更长，且在索拉非尼治疗后更有可能接受进一步治疗。这表明序贯接受多线治疗对OS有递增益处，证明了对符合条件的患者进行治疗阶段迁移是合理的。
