Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis

Objective: REACH-2 and REACH were randomized, placebo-controlled, double-blind, multicenter phase 3 trials which showed survival benefits of ramucirumab treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP). We evaluated the efficacy and safety of ramucirumab in Asian and non-Asian patients with AFP ≥400 ng/mL from REACH-2 and REACH. Methods: We pooled Asian and non-Asian patients from the REACH-2 and REACH trials and performed an individual patient data meta-analysis. Overall survival (OS) and progression-free survival were evaluated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated with a stratified Cox regression model. Results: In the pooled REACH-2 and REACH patient population, 291 Asian patients were randomly assigned to receive ramucirumab (n = 168) or placebo (n = 123), and 251 non-Asian patients received ramucirumab (n = 148) or placebo (n = 103). The median OS was significantly longer in the ramucirumab arm in comparison to the placebo arm for Asian patients (8.08 vs. 4.76 months, stratified HR 0.73 [95% CI 0.56–0.95], p = 0.0189) and non-Asian patients (7.98 vs. 5.22 months, stratified HR 0.65 [95% CI 0.49–0.86], p = 0.0028). The overall response rate (ORR) and disease control rate (DCR) were significantly higher in the ramucirumab arm compared to the placebo arm for Asian patients (ORR: 4.2 vs. 0.8%; DCR: 53.6 vs. 33.3%) and non-Asian patients (ORR: 6.8 vs. 1.0%; DCR: 59.5 vs. 41.7%). The most common grade ≥3 treatment-emergent adverse events reported in the ramucirumab arm were hypertension (7.7%), decreased appetite (1.2%), and ascites (1.2%) for Asian patients and hypertension (16.9%), ascites (8.8%), asthenia (4.7%), and fatigue (5.4%) for non-Asian patients. Discussion and Conclusion: This pooled analysis of the REACH-2/REACH trials demonstrates significant benefits, with a manageable safety profile, of ramucirumab treatment in Asian and non-Asian patients with advanced HCC and baseline AFP ≥400 ng/mL.

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Prognostic and clinicopathological significance of PD-1 expression in hepatocellular carcinoma: a meta-analysis

Journal of International Medical Research ◽

10.1177/0300060520962675 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052096267

Author(s):

Qian Zhang ◽

Kexiang Zhou ◽

Wei Liang ◽

Wei Xiong

Keyword(s):

Hepatocellular Carcinoma ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Stage ◽

Alpha Fetoprotein ◽

Biomedical Literature ◽

Free Survival ◽

Programmed Cell Death 1 ◽

Clinicopathological Significance ◽

Disease Free

Objective We performed a meta-analysis to evaluate the prognostic and clinicopathological significance of programmed cell death-1 (PD-1) expression in patients with hepatocellular carcinoma (HCC). Methods We searched the Wanfang, Chinese Biomedical Literature, CNKI, PubMed, Embase, and Web of Science databases for relevant articles from inception to 1 July 2020. Statistical analysis was performed using RevMan 5.3 (Cochrane, London, UK) and Stata 14.0 software (StataCorp LP, College Station, TX, USA). Results Eight studies involving 732 patients with HCC were included. Higher expression of PD-1 predicted longer disease-free survival [hazard ratio (HR) 0.53, 95% confidence interval (CI): 0.38–0.72]. No significant correlation was observed between PD-1 expression and overall survival (HR 0.89, 95% CI: 0.58–1.35). PD-1 expression was correlated with age [odds ratio (OR) 0.66, 95% CI: 0.46–0.94] and alpha-fetoprotein level (OR 2.27, 95% CI: 1.45–3.55); no correlation was observed with sex, tumor size, tumor metastasis, hepatitis B virus history, tumor stage, or tumor multiplicity. Sensitivity analysis demonstrated no excessive effect on stability of the pooled results. No significant publication bias was found among the identified studies. Conclusion PD-1 overexpression predicted better disease-free survival in patients with HCC. Moreover, PD-1 expression was associated with age and alpha-fetoprotein level.

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