Anti-PD-1therapy Combined With Thermal Ablation for Advanced HCC
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional
Phase: Phase 2

Summary: 
      The inhibition of programmed cell death protein 1 (PD-1) has shown promising antitumor
      activity in advanced hepatocellular carcinoma (HCC). Unfortunately, less than 20% of HCC have
      response. The effect of PD-1 blockade and incomplete thermal ablation in patients with
      advanced HCC is not yet clearly understood. This study aimed to analyze outcomes of advanced
      HCC treated with anti PD-1 inhibitors in combination with incomplete thermal ablation.
    

Detailed description: 
      Hepatocellular carcinoma (HCC) is ranked as the third leading cause of cancer death both
      worldwide and in the China. In the past decade, survivals of patients with advanced HCC or
      those who have progressed diseases following locoregional treatments can be increased with
      the multi-kinase inhibitor sorafenib, the first evidence identified drug for HCC. Recent
      clinical trials further verified some novel tyrosine kinase inhibitors such as regorafenib
      and cabozantinib, and two programmed cell death protein-1 (PD-1) immune checkpoint inhibitors
      (ICIs), nivolumab and pembrolizumab, as useful therapies in second line setting following
      sorafenib.

      Advances in programmed cell death protein 1 (PD-1) blockade have shown an ORR of 15-17% and
      median survival time of 12.9-15.0 months among patients with advanced HCC. Of these,
      nivolumab and pembrolizumab have been accelerated approved as second-line treatment of
      advanced HCC. Notably, patients who have tumor responses maintain long-lasting disease
      control for 9.9-17months and still a large proportion of patients (81-83%) do not respond to
      mono PD-1 blockade, which emphasizing the need to explore strategies to increase the efficacy
      of immunotherapy.

      An approach to expanding the benefit of ICIs may involve combinations with locoregional
      therapy like radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), such
      treatments have been shown to boost tumor-specific T-cell response through release of TAAs
      from HCC cells. The intent-to-treat population of this study was a subset of patients
      receiving ongoing ICIs therapy for advanced HCC and is with stable disease or atypical
      responses in different lesions of the same individuals.
    

Intervention name(s): pembrolizumab or nivolumab or JS001
Intervention type(s): Drug
Intervention description(s): ICIs therapy of nivolumab (3 mg/kg, per 2 weeks) or pembrolizumab (2 mg/kg, per 3 weeks) or JS001 (240mg, per 3 weeks) was performed until the off-treatment criteria were met. For participants with stable disease or atypical progression to ICIs therapy, thermal ablation of radiofrequency ablation or microwave ablation was performed addtionally.
Other intervention name(s): computed tomography guided radiofrequency ablation; or computed tomography guided microwave ablation
Intervention MeSH terms: Pembrolizumab; Nivolumab
Intervention model: Single Group Assignment
Intervention model description: The study subjects were those who with advanced HCC that progressed on first-line sorafenib and treated with anti-PD-1 therapy in combination with incomplete thermal ablation.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hepatocellular carcinoma; Immunotherapy; Nivolumab; Pembrolizumab; Radiofrequency Ablation; Microwave ablation