1. Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2
- Author
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Reigetsu Yoshikawa, Peter R. Galle, Chunxiao Wang, Arndt Vogel, Kenta Shinozaki, Richard S. Finn, Yi Hsiang Huang, Yoon-Koo Kang, Stephen L. Chan, Daniel H. Palmer, Giovanni Brandi, Eric Assenat, Chia Jui Yen, Masatoshi Kudo, Masafumi Ikeda, Philippe Merle, Ryan C. Widau, Paolo Abada, Tatsuya Yamashita, Andrew X. Zhu, Josep M. Llovet, Kudo M., Galle P.R., Brandi G., Kang Y.-K., Yen C.-J., Finn R.S., Llovet J.M., Assenat E., Merle P., Chan S.L., Palmer D.H., Ikeda M., Yamashita T., Vogel A., Huang Y.-H., Abada P.B., Yoshikawa R., Shinozaki K., Wang C., Widau R.C., and Zhu A.X.
- Subjects
Nomografia (Matemàtica) ,Survival ,Tumour response ,AST, aspartate aminotransferase ,ALBI ,ITT, intent-to-treat ,Gastroenterology ,EoT, end of treatment ,PR, partial response ,Albúmines ,Immunology and Allergy ,ALBI, albumin–bilirubin ,education.field_of_study ,AFP, alpha-fetoprotein ,Hazard ratio ,BCLC, Barcelona Clinic Liver Cancer ,Prognosis ,VEGF, vascular endothelial growth factor ,CR, complete response ,Safety ,AE, adverse event ,Liver cancer ,VEGFRs, vascular endothelial growth factor receptors ,Research Article ,medicine.medical_specialty ,PD, progressive disease ,Prognosi ,Population ,IQR, inter-quartile range ,Placebo ,Liver function ,Ramucirumab ,OS, overall survival ,Càncer de fetge ,Nomography (Mathematics) ,CP, Child-Pugh ,ALT, alanine aminotransferase ,Albumins ,Internal medicine ,Internal Medicine ,medicine ,lcsh:RC799-869 ,BSC, best supportive care ,education ,Intention-to-treat analysis ,Ram, ramucirumab ,Hepatology ,GGT, gamma-glutamyltransferase ,business.industry ,TACE, transarterial chemoembolisation ,SD, stable disease ,ECOG PS, Eastern Cooperative Oncology Group performance status ,Nomogram ,medicine.disease ,HR, hazard ratio ,MVI, macrovascular invasion ,AESI, adverse event of special interest ,lcsh:Diseases of the digestive system. Gastroenterology ,HCC, hepatocellular carcinoma ,business ,BOR, best overall response ,Progressive disease - Abstract
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., Graphical abstract, Highlights • In patients with HCC, the severity of coexisting liver dysfunction is usually categorised using the Child-Pugh system. • We demonstrate that the simpler albumin–bilirubin (ALBI) nomogram can be used for pre-treatment prognostication and on-treatment assessment. • Ramucirumab did not negatively impact on liver function compared to placebo in patients with advanced HCC and elevated AFP. • Liver-specific adverse events were reported more frequently in patients with more severe liver disfunction at baseline. • Ramucirumab provided a survival benefit irrespective of baseline liver function in patients with advanced HCC and elevated AFP.
- Published
- 2021