Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

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.

ALBI grade: Evidence for an improved model for liver functional estimation in patients with hepatocellular carcinoma

“…In particular, in 2 post hoc analyses conducted on patients treated with cabozantinib and ramucirumab in the CELESTIAL and REACH-2 trials, respectively, a more favourable ALBI grade correlated with improved OS and progression-free survival following treatment. 86 , 87 Besides, treatment-related adverse events were observed less frequently in patients with lower ALBI grade (I vs. II-III). For CP-B patients treated with regorafenib, a higher ALBI grade (III vs. I-II) predicted significantly poorer survival.…”

“… Kudo et al. 87 RCT, phase III (REACH and REACH-II) 857 Ramucirumab/placebo (n = 480/377) Low baseline ALBI grade (I vs . II-III) independently predicted favourable OS.…”

The third year

“…Dr Kudo and colleagues describe the use of the ALBI score in evaluating HCC patients on treatment with ramicirumab. 7 The results of this study are, to me, less interesting than the fact that they are using the ALBI score. The use of this score is becoming widespread.…”

Sequential Therapy for Hepatocellular Carcinoma after Failure of Atezolizumab plus Bevacizumab Combination Therapy

“…Furthermore, and from a different perspective, ramucirumab may be a candidate for second-line therapy when serum AFP level is ≥400 ng/mL. Since ramucirumab does not impair liver function and quality of life [47,48], its use as a second-line treatment after atezolizumab plus bevacizumab may offer patients a better quality of life, with fewer adverse events, while maintaining stable dis-ease even in elderly patients. Furthermore, recent report by Finn et al [49] showed that ramucirumab achieved ORR of 16.7% (4 of 24 cases) in patients who failed prior PD-1/PD-L1 antibody therapies (nivolumab in 3 and durvalumab plus tremelimumab in 1) in the REACH-2 Open-Label Expansion Cohort, suggesting that ramucirumab may be effective after ICI therapy.…”