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2016 ESMO世界胃肠肿瘤大会（GI）于6月29日至7月2日在西班牙巴塞罗那召开。ESMOGI涉及胃肠道的各个部分，涵盖了众多常见和不常见肿瘤的筛查、诊断和治疗进展，是胃肠恶性肿瘤领域的世界级盛会。
第18届 ESMO GI大会最新突破性研究（Late Breaking Abstracts）LBA03关注了肝癌靶向的新未来。该RESORCE研究是一项随机双盲、安慰剂对照的Ⅲ期临床研究，由国际多个机构共同参与，其中包括我国的南京八一医院、天津肿瘤医院、第四军医大学西京医院和台湾荣民总医院。
肝癌的系统治疗长期没有突破，过去的10年间许多有潜力的药物前赴后继但最终都折戟沉沙，仅存
主要研究内容
RESORCE研究中的肝癌患者需要满足：
◆巴塞罗那分期（BCLC）B或C；
◆索拉非尼治疗≥20天，剂量≥400mg/d；
◆影像学证实疾病进展；
◆Child-Pugh肝功能分级A；
◆ECOG PS 0-1；
21个国家共入组573名HCC患者，按2:1随机分配进瑞格非尼160mg组（379例）或安慰剂组（194例），1-3周每日一次，四周为一周期。根据基线人口统计学数据和疾病参数进行随机化。
所有患者都给与最佳支持治疗，治疗持续直到患者疾病进展、死亡或不能耐受毒性。
主要终点为总生存（OS，意向性分析）、次要终点包括无进展生存（PFS）、至疾病进展时间（TTP）、缓解率（RR）和疾病控制率（DCR）。
主要结果
对于所有患者，中位年龄63岁，88%为男性，且87%为BCLC分期C。
◆中位治疗持续时间瑞格非尼为3.6个月，而安慰剂仅有1.9个月。瑞格非尼治疗组与安慰剂相比，死亡风险下降38%（HR=0.62）。
◆中位总生存（OS）期瑞格非尼组为10.6个月，而安慰剂组仅有7.8个月。瑞格非尼组与安慰剂相比，疾病进展或死亡风险下降54%（HR=0.46）。
◆中位无进展生存（PFS）期瑞格非尼组为3.1个月，而安慰剂组仅有1.5个月。
◆中位至疾病进展时间（TTP）瑞格非尼组为3.2个月，而安慰剂组仅有1.5个月（HR=0.44）。
◆疾病控制率（DCR=完全缓解+部分缓解+疾病稳定）瑞格非尼组为65.2%，而安慰剂组仅有36.1%。
◆总缓解率（完全缓解+部分缓解）瑞格非尼组为10.6%，而安慰剂组仅有4.1%。
3级以上不良事件发生率，瑞格非尼组为79.7%，安慰剂组为58.5%。
最常见的3级以上不良事件在瑞格非尼组和安慰剂组分别为高血压（15.2% vs 4.7%）、手足皮肤反应（12.6% vs 0.5%）、乏力（9.1% vs 4.7%）和
因不良事件而调整治疗剂量的发生率在瑞格非尼组和安慰剂组分别为68.2% vs 31.1%。最后一次治疗30天后死亡率安慰剂组稍高于瑞格非尼组，分别为19.7% vs 13.4%。
结论
RESORCE证实了瑞格非尼能够显著改善索拉非尼经治失败肝细胞癌患者的总生存，不良事件发生率与前期安全性评价相吻合。虽然没有发现瑞格非尼的临床获益对肿瘤分期和致病原因有所挑剔，但是生物标志物分析将有可能解释哪种亚组的患者获益更多。瑞格非尼作为有效的二线治疗手段，为肝癌患者提供了新的选择。
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摘要阅读：
LBA-03
Efficacy and safety of regorafenibversus placebo in patients with hepatocellular carcinoma (HCC) progressing onsorafenib: Results of the international, randomized phase 3 RESORCE trial
Background:Thereare no proven or approved second-line treatment options for patients withadvanced HCC. Based on promising activity in a second-line phase 2 study(Bruix, Eur J Cancer 2013), we evaluated regorafenib, an oral multikinaseinhibitor, in patients with intermediate or advanced HCC who had diseaseprogression on sorafenib.
Methods:In this double-blind, placebo-controlled trial, adults with HCC BarcelonaClinic Liver Cancer (BCLC) stage B or C who received sorafenib for ≥20days at ≥400 mg/day and had documentedradiological progression on sorafenib, Child-Pugh A liver function, and ECOGperformance status 0-1 were randomized 2:1 (stratification by geographic regionAsia vs rest of the world, performance status, alpha-fetoprotein, extrahepaticspread, macroscopic vascular invasion) to regorafenib 160 mg or placebo oncedaily during weeks 1–3 of each 4-week cycle. All received best supportive care.Treatment continued until disease progression, death, or unacceptable toxicity.The primary endpoint of overall survival (OS) was analyzed by intent-to-treat.Secondary endpoints were progression-free survival (PFS), time-to-progression(TTP), response rate (RR), and disease control rate (DCR).
Results:Thetrial was conducted in 21 countries and a total of 573 patients were randomized(regorafenib=379; placebo=194). Baseline demographic and diseasecharacteristics were balanced between arms. For all patients, median age was 63years, 88% were male, and 87% were BCLC stage C. Median (range) treatmentduration was 3.6 months (0.03‒29.4) for regorafenib and 1.9 months (0.2‒27.4)for placebo. The regorafenib group had a 38% reduction in the risk of death (HR0.62; 95%CI 0.50‒0.78; p <0.001); median OS (regorafenib vs placebo) was10.6 vs 7.8 months. There was a 54% reduction in the risk of progression ordeath with regorafenib (HR 0.46; 95%CI 0.37‒0.56; p <0.001); median PFS(regorafenib vs placebo) was 3.1 vs 1.5 months. Median TTP (regorafenib vsplacebo) was 3.2 vs 1.5 months (HR 0.44; 95%CI 0.36–0.55; p<0.001). DCR(complete and partial responses + stable disease by mRECIST) for regorafenib vsplacebo was 65.2% vs 36.1% (p<0.001). Overall RRs (complete and partialresponses) were 10.6% vs 4.1% (p=0.005), respectively. Rates of grade ≥3adverse events were 79.7% with regorafenib and 58.5% with placebo. Most commongrade ≥3adverse events occurring more frequently in the regorafenib group included(regorafenib vs placebo) hypertension (15.2% vs 4.7%), hand-foot skin reaction(12.6% vs 0.5%), fatigue (9.1% vs 4.7%), and diarrhea (3.2% vs 0%). Rates ofdose modifications due to adverse events were 68.2% with regorafenib and 31.1%with placebo. Deaths occurring up to 30 days after last dose of study drug werehigher in the placebo group (13.4% regorafenib, 19.7% placebo).
Conclusions:Regorafenibsignificantly improved OS in patients with HCC who progressed during treatmentwith sorafenib. Adverse events were consistent with the known safety profile ofregorafenib.
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文献：Jordi Bruix.et al.Ann Oncol (2016) 27(suppl 2): ii140-ii141
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