Phase II Study of Avelumab in Patients with Advanced Hepatocellular Carcinoma Previously Treated with Sorafenib

Clin Cancer Res. 2021 Feb 1;27(3):713-718. doi: 10.1158/1078-0432.CCR-20-3094. Epub 2020 Nov 2.

Abstract

Purpose: This study investigated the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with advanced hepatocellular carcinoma previously treated with sorafenib (NCT03389126).

Patients and methods: This is a single-arm, single center, phase II trial. Patients with Child-Pugh A score who had at least one measurable lesion were enrolled. Intravenous avelumab 10 mg/kg every 2 weeks was given until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to RECIST v1.1. Secondary endpoints included time to progression (TTP), overall survival (OS), disease control rate (DCR), and safety.

Results: A total of 30 patients were enrolled. After a median follow-up of 13.9 months, 27 progression events and 20 death events occurred. There was no complete response, three (10.0%) partial responses, and 19 patients (63.3%) with stable disease. ORR was 10.0% and DCR was 73.3%. The median TTP and OS was 4.4 and 14.2 months, respectively. PD-L1 expression did not affect avelumab response. Prior duration of sorafenib treatment, when dichotomized by the median 2.7 months, was associated with treatment outcome. TTP (6.5 vs. 1.8 months, P = 0.007) and OS (19.0 vs. 7.8 months, P = 0.006) were superior in patients with longer sorafenib duration. There was tendency of higher ORR (20.0% vs. 0.0%, P = 0.22) in those with longer sorafenib duration. Avelumab was well tolerated with seven grade 3 adverse events and no grade 4 adverse events.

Conclusions: Avelumab showed moderate efficacy and was well tolerated in advanced hepatocellular carcinoma previously treated with sorafenib.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Response Evaluation Criteria in Solid Tumors
  • Sorafenib / pharmacology*
  • Sorafenib / therapeutic use
  • Time Factors

Substances

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • CD274 protein, human
  • Sorafenib
  • avelumab

Associated data

  • ClinicalTrials.gov/NCT03389126