AASLD2018[270]Ramucirumab作为二线治疗 在肝细胞癌患者中 （HCC）

StephenW

270
Ramucirumab As Second-Line Treatment
in Patients with Hepatocellular Carcinoma
(HCC) and Elevated Alpha-Fetoprotein (AFP)
Following Sorafenib: Pooled Results from Two
Global Phase 3 Studies (REACH-2 and REACH)
Josep M Llovet1, Masatoshi Kudo2, Richard Finn3, Peter R.
Galle4, Jean-Frederic Blanc5, Takuji Okusaka6, Ian Chau7,
Paolo B Abada8, Yanzhi Hsu8 and Andrew X Zhu9, (1)Icahn
School of Medicine at Mount Sinai, (2)Kindai University,
(3)University of California, (4)Department of Medicine I,
University Medical Center Mainz, Germany, (5)CHU De
Bordeaux, Hôpital Haut-Lévêque, (6)National Cancer Center
Hospital, (7)Royal Marsden Hospital, (8)Eli Lilly and Company,
(9)Massachusetts General Hospital, Harvard Medical Center
Background: Ramucirumab (RAM), a human IgG1
monoclonal antibody, inhibits activation of VEGFR2.
REACH-2 and REACH were two randomized, global, blinded,
phase 3 studies of RAM vs palcebo (PL) in patients (pts)
with HCC after prior sorafenib. REACH-2 was designed to
confirmed the benefit of RAM in the pre-specified population
of pts with baseline AFP ≥400 ng/mL observed in REACH.
The primary endpoint of REACH-2 was met demonstrating an
improved overall survival (OS), and RAM was well tolerated.
Pooled analyses of pts from REACH-2 (292) and REACH
(250) with baseline AFP ≥400 ng/mL were performed (N=316
RAM vs N=226 PL) Methods: With the exception of AFP
level, REACH-2 and REACH eligibility were similar, enrolling
HCC pts with BCLC stage C or B refractory/not amenable
to locoregional therapy, ECOG PS 0 or 1, Child-Pugh <7;
disease progression on or intolerance to sorafenib, and
adequate lab parameters. Pts received IV RAM (8 mg/kg) or
PL every 14 days and were treated until disease progression
or unacceptable toxicity. Pooled analyses were performed
at the individual pt level, stratified by study, and assessed
OS, progression-free survival (PFS), objective response rate
(ORR), safety, and pt reported symptoms (FACT-Hepatobiliary
Symptom Index-8 [FSHI-8]). Results: Pooled baseline pt
characteristics were balanced between arms including ECOG
PS, presence of macrovascular invasion, and baseline AFP.
RAM treatment significantly improved OS (median OS 8.1
mo vs 5.0 mo PL; HR 0.694; 95% CI 0.571, 0.842; p=.0002).
Improvements were observed in PFS (median PFS 2.8 mo vs
1.5 mo PL; HR 0.572; 95% CI 0.472, 0.694; p<.0001), ORR
(5.4% RAM vs 0.9% PL [p=.0040]), and disease control rate
(ORR + stable disease = 56.3% RAM vs 37.2% PL [p<.0001]).
Dose intensity was 98.3% RAM vs 99.6% PL. 9.5% of pts on
the RAM arm vs 3.6% on PL discontinued study treatment
due to treatment-related adverse events (AEs). Hypertension
(12.0% vs 3.6% PL) and hyponatremia (5.1% vs 2.2% PL)
were the only Grade (G) ≥3 treatment-emergent AEs occurring
in ≥5% in RAM. RAM treatment significantly delayed time to
deterioration of FHSI-8 (p=0.0152), including individual items
of back pain, weight loss, and pain. Conclusion: A pooled
analysis of two phase 3 trials assessing RAM as second-line
treatment in pts with HCC following first-line sorafenib and
AFP ≥400 ng/mL (REACH-2 and REACH) demonstrates a
significant and clinically meaningful benefit with a favorable
safety profile, including a benefit in pt-reported outcomes.

StephenW

270
Ramucirumab作为二线治疗
在肝细胞癌患者中
（HCC）和升高的甲胎蛋白（AFP）
索拉非尼之后：两个人的汇总结果
全球第3阶段研究（REACH-2和REACH）
何塞普中号Llovet1，正敏Kudo2，理查德Finn3，彼得R.
Galle4，让 - 弗雷德里克Blanc5，卓尔Okusaka6，伊恩Chau7，
保罗乙Abada8，胭脂Hsu8和Andrew X Zhu9，（1）爱康
西奈山医学院，（2）Kindai大学，
（3）加州大学（4）医学系I，
德国美因茨大学医学中心，（5）褚德
波尔多，总医院的Haut-莱韦克塔，（6）国立癌症中心
医院，（7）皇家马斯登医院，（8）礼来公司，
（9）马萨诸塞州综合医院，哈佛医疗中心
背景：Ramucirumab（RAM），人IgG1
单克隆抗体，抑制VEGFR2的激活。
REACH-2和REACH是两个随机的，全球性的，不知情的，
患者RAM与palcebo（PL）的3期研究（pts）
先前使用索拉非尼治疗后发生HCC。 REACH-2的目的是为了
确认了RAM在预先指定的人群中的好处
在REACH中观察到基线AFP≥400ng/ mL的患者。
REACH-2的主要终点得到满足，证明了这一点
提高了整体存活率（OS），并且RAM的耐受性良好。
对REACH-2（292）和REACH的pts进行汇总分析
（250）进行基线AFP≥400ng/ mL（N = 316
RAM与N = 226 PL）方法：AFP除外
水平，REACH-2和REACH资格相似，滚动
HCC患有BCLC C期或B期难治性/不适合
局部治疗，ECOG PS 0或1，Child-Pugh <7;
索拉非尼的疾病进展或不耐受，和
足够的实验参数患者接受IV RAM（8 mg / kg）或
PL每14天进行治疗直至疾病进展
或不可接受的毒性。进行汇总分析
在个人pt水平，按研究分层，并进行评估
OS，无进展生存期（PFS），客观反应率
（ORR），安全性和pt报告的症状（FACT-Hepatobiliary
症状指数-8 [FSHI-8]）。结果：合并基线pt
包括ECOG在内的武器之间的特征是平衡的
PS，存在大血管侵犯和基线AFP。
RAM处理显着改善了OS（媒体OS 8.1
mo vs 5.0 mo PL; HR 0.694; 95％CI 0.571,0.842; p = .0002）。
在PFS中观察到改善（测量的PFS 2.8 mo vs.
1.5米或PL; HR 0.572; 95％CI 0.472,0.694; p <.0001），ORR
（5.4％RAM对0.9％PL [p = .0040]）和疾病控制率
（ORR +稳定疾病= 56.3％RAM对37.2％PL [p <.0001]）。
剂量强度为98.3％RAM对比99.6％PL。 9.5％的人
RAM手臂与PL停止研究治疗的3.6％相比
由于治疗相关的不良事件（AEs）。高血压
（12.0％vs 3.6％PL）和低钠血症（5.1％vs 2.2％PL）
是唯一发生≥（3）级治疗急症的AEs
在RAM中≥5％。 RAM处理显着延迟了时间
FHSI-8恶化（p = 0.0152），包括个别项目
背痛，体重减轻和疼痛。结论：汇总
分析两个阶段3试验评估RAM作为二线
一线索拉非尼治疗HCC治疗
AFP≥400ng/ mL（REACH-2和REACH）表明a
具有显着和临床意义的有益效益
安全概况，包括pt报告结果的好处.