Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2
Masatoshi Kudo,
Peter R. Galle,
Giovanni Brandi,
Yoon-Koo Kang,
Chia-Jui Yen,
Richard S. Finn,
Josep M. Llovet,
Eric Assenat,
Philippe Merle,
Stephen L. Chan,
Daniel H. Palmer,
Masafumi Ikeda,
Tatsuya Yamashita,
Arndt Vogel,
Yi-Hsiang Huang,
Paolo B. Abada,
Reigetsu Yoshikawa,
Kenta Shinozaki,
Chunxiao Wang,
Ryan C. Widau,
Andrew X. Zhu
Affiliations
Masatoshi Kudo
Department of Gastroenterology and Hepatology, Kindai University, Osaka-Sayama, Japan; Corresponding authors. Addresses: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama City, Osaka, 589-8511, Japan. Tel.: +81 72 366 0221.
Peter R. Galle
Medizinische Klinik und Poliklinik, University Medical Center, Mainz, Germany
Giovanni Brandi
Department of Experimental, Diagnostic and Specialty Medicine, Saint Orsola Malpighi Hospital, University of Bologna, Bologna, Italy
Yoon-Koo Kang
Department of Oncology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea
Chia-Jui Yen
Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Richard S. Finn
Division of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Josep M. Llovet
Icahn School of Medicine at Mount Sinai, New York, NY, USA; Institut d´Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain
Eric Assenat
Département d'oncologie médicale, CHU de Montpellier, Montpellier, France
Philippe Merle
Hepatology and Gastroenterology Unit, Hôpital de la Croix Rousse, Lyon, France
Stephen L. Chan
State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong, People's Republic of China; Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong, People's Republic of China
Daniel H. Palmer
Molecular and Clinical Cancer Medicine, Clatterbridge Cancer Centre, University of Liverpool, Bebington, Wirral, UK
Masafumi Ikeda
Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
Tatsuya Yamashita
Department of Gastroenterology, Kanazawa University Hospital, Ishikawa, Japan
Arndt Vogel
Klinik für Gastroenterologie, Hepatologie and Endokrinologie, Hannover Medical School, Hannover, Germany
Yi-Hsiang Huang
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Paolo B. Abada
Eli Lilly and Company, Indianapolis, Indiana, USA
Reigetsu Yoshikawa
Eli Lilly Japan KK, Kobe, Hyogo, Japan
Kenta Shinozaki
Eli Lilly Japan KK, Kobe, Hyogo, Japan
Chunxiao Wang
Eli Lilly and Company, Indianapolis, Indiana, USA
Ryan C. Widau
Eli Lilly and Company, Indianapolis, Indiana, USA
Andrew X. Zhu
Massachusetts General Hospital Cancer Center, Harvard Medical Center, Boston, MA, USA; Liver Cancer Research, Massachusetts General Hospital Cancer Center, 52 Fruit Street, Boston, MA 02115, USA.
Background & Aims: The albumin–bilirubin (ALBI) grade/score is derived from a validated nomogram to objectively assess prognosis and liver function in patients with hepatocellular carcinoma (HCC). In this post hoc analysis, we assessed prognosis in terms of survival by baseline ALBI grade and monitored liver function during treatment with ramucirumab or placebo using the ALBI score in patients with advanced HCC. Methods: Patients with advanced HCC, Child-Pugh class A with prior sorafenib treatment were randomised in REACH trials to receive ramucirumab 8 mg/kg or placebo every 2 weeks. Data were analysed by trial and as a meta-analysis of individual patient-level data (pooled population) from REACH (alpha-fetoprotein ≥400 ng/ml) and REACH-2. Patients from REACH with Child-Pugh class B were analysed as a separate cohort. The ALBI grades and scores were calculated at baseline and before each treatment cycle. Results: Baseline characteristics by ALBI grade were balanced between treatment arms among patients in the pooled population (ALBI-1, n = 231; ALBI-2, n = 296; ALBI-3, n = 7). Baseline ALBI grade was prognostic for overall survival (OS; ALBI grade 2 vs. 1; hazard ratio [HR]: 1.38 [1.13–1.69]), after adjusting for other significant prognostic factors. Mean ALBI scores remained stable in both treatment arms compared with baseline and were unaffected by baseline ALBI grade, macrovascular invasion, tumour response, geographical region, or prior locoregional therapy. Baseline ALBI grades 2 and 3 were associated with increased incidence of liver-specific adverse events and discontinuation rates in both treatments. Ramucirumab improved OS in patients with baseline ALBI grade 1 (HR 0.605 [0.445–0.824]) and ALBI grade 2 (HR 0.814 [0.630–1.051]). Conclusions: Compared with placebo, ramucirumab did not negatively impact liver function and improved survival irrespective of baseline ALBI grade. Lay summary: Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide. Prognosis is affected by many clinical factors including liver function both before and during anticancer treatment. Here we have used a validated approach to assess liver function using 2 laboratory parameters, serum albumin and bilirubin (ALBI), both before and during treatment with ramucirumab in 2 phase III placebo-controlled studies. We confirm the practicality of using this more simplistic approach in assessing liver function prior to and during anticancer therapy, and demonstrate ramucirumab did not impair liver function when compared with placebo.
