Send to

Choose Destination
JAMA Oncol. 2017 Feb 1;3(2):235-243. doi: 10.1001/jamaoncol.2016.4115.

Ramucirumab as Second-Line Treatment in Patients With Advanced Hepatocellular Carcinoma: Analysis of REACH Trial Results by Child-Pugh Score.

Author information

Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston.
California Pacific Medical Center, San Francisco.
Otto von Guericke University of Magdeburg, Magdeburg, Germany.
Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan.
Saga-Ken Medical Centre Koseikan, Saga, Japan.
Surgery Department CHU Estaing, Clermond Ferrand, France.
Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany.
Policlinico Sant' Orsola-Malpighi, Bologna, Italy.
Catholic University of Sacred Heart, Rome, Italy.
Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Gangnam Severance Hospital, Seoul, South Korea.
Yonsei Cancer Center, Cancer Metastasis Research Center, Yonsei University College of Medicine, Shinchon-Dong, South Korea.
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan17National Yang-Ming University School of Medicine, Taipei, Taiwan.
National Cheng Kung University Hospital, Tainan City, Taiwan.
Chang Gung Memorial Hospital, Chiayi, Taiwan.
Eli Lilly and Company, Bridgewater, New Jersey.
AstraZeneca Pharmaceuticals, Wilmington, Delaware.
Eli Lilly and Company, Indianapolis, Indiana.
Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.



REACH is the first phase 3 trial to provide information on hepatocellular cancer (HCC) in the second-line (postsorafenib) setting categorized by Child-Pugh score, a scoring system used to measure the severity of chronic liver disease. This exploratory analysis demonstrates the relationship between a potential ramucirumab survival benefit, severity of liver disease, and baseline α-fetoprotein (αFP).


To assess treatment effects and tolerability of ramucirumab by Child-Pugh score in patients with HCC enrolled in the REACH trial.

Design, Settings, and Participants:

Randomized, double-blind, phase 3 trial of ramucirumab and best supportive care vs placebo and best supportive care as second-line treatment in patients with HCC enrolled between November 4, 2010 and April 18, 2013, from 154 global sites. Overall, 643 patients were randomized and included in this analysis; 565 patients considered Child-Pugh class A (Child-Pugh scores 5 and 6) and 78 patients considered class B (Child-Pugh scores 7 and 8).


Ramucirumab (8 mg/kg) or placebo intravenously plus best supportive care every 2 weeks.

Main Outcomes and Measures:

Overall survival (OS), defined as time from randomization to death from any cause.


In the randomized population of 643 patients (mean [SD] age, 62.8 [11.1] years) in this analysis, a potential ramucirumab OS benefit was observed for patients with a Child-Pugh score of 5 (hazard ratio [HR], 0.80; 95% CI, 0.63-1.02; P = .06) but no apparent benefit for patients with Child-Pugh scores of 6 or 7 and 8. In patients with baseline αFP levels of 400 ng/mL (to convert ng/mL to μg/L, multiply by 1.0) or more, a ramucirumab OS benefit was significant for a score of Child-Pugh 5 (HR, 0.61; 95% CI, 0.43-0.87; P = .01) and Child-Pugh 6 (HR, 0.64; 95% CI, 0.42-0.98; P = .04), but was not significant for Child-Pugh 7 and 8. The overall safety profile of ramucirumab, regardless of Child-Pugh score, was considered manageable. Regardless of treatment arm, patients with Child-Pugh scores of 7 and 8 experienced a higher incidence of grade 3 or higher treatment-emergent adverse events, including ascites and asthenia, and special-interest events, including liver injury and/or failure and bleeding, compared with patients with Child-Pugh scores of 5 or 6.

Conclusions and Relevance:

In unselected patients, a trend for ramucirumab survival benefit was observed only for patients with a Child-Pugh score of 5. In patients with baseline αFP levels of 400 ng/mL or more, a ramucirumab survival benefit was observed for Child-Pugh scores of 5 and 6. Ramucirumab had a manageable toxic effect profile. These results support the ongoing REACH-2 study of ramucirumab in patients with advanced HCC with underlying Child-Pugh A cirrhosis and baseline αFP levels of 400 ng/mL or more.

Trial Registration: Identifier: NCT01140347.

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center