Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients

Xuqi Sun,Ziliang Yang,Wenping Lin,Jie Mei,Wei Peng,Jinbin Chen,Li Xu,Minshan Chen,Yaojun Zhang

doi:10.1186/s12885-021-08428-w

Xuqi Sun, Ziliang Yang + Show 7 more

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https://doi.org/10.1186/s12885-021-08428-w

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Abstract

BackgroundFew biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy.MethodsA total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS.ResultsAmong all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006).ConclusionEarly reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.

Highlights

Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancies and fourth leading cause of cancer-related mortality worldwide [1, 2]
After 6 weeks of anti-programmed death 1 (PD-1) immunotherapy, the AFP level of 48.1% (113/235) of patients decreased by more than 50% from baseline, and the PIVKA-II level of 53.2% (125/ 235) of patients decreased by more than 50% from baseline
7.7% (18/235) received antiPD-1 therapy as monotherapy, 22.1% (52/235) received anti-Progressive disease (PD)-1 therapy plus targeted drugs, 30.2% (71/235) received anti-PD-1 therapy plus locoregional treatments, including transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy, and 40.0% (94/235) received anti-PD-1 therapy combined with targeted drugs and locoregional treatments

Summary

Introduction

Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancies and fourth leading cause of cancer-related mortality worldwide [1, 2]. Sorafenib and lenvatinib are approved as the first-line treatment for advanced HCC, the survival of these patients remains dismal [5]. The emergence of anti-programmed death 1 (PD-1) checkpoint inhibitors has changed the landscape of systemic treatments for advanced HCC. The objective response rates (ORRs) can reach to 17–20% in advanced HCC patients who receive anti-PD-1 therapy as monotherapy [6, 7]. The combination of atezolizumab and bevacizumab (A + T) achieved significantly longer survival in HCC patients than sorafenib, which increased. Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy

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