Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR) Combined With Fecal Microbiota Transplantation (FMT) for Reversing Resistance to First-Line Targeted-Immunotherapy in Advanced HCC: A Clinical Application Study
This is an open-label, multicenter, randomized controlled Phase II trial. Patients with advanced hepatocellular carcinoma (HCC) who developed secondary resistance to first-line targeted-immunotherapy were randomly assigned to receive either the original first-line targeted-immunotherapy combined with FMT and PULSAR (experimental group), or second-line targeted-immunotherapy (control group). The first-line targeted-immunotherapy regimens consisted of tislelizumab combined with one of the first-line evidence-based tyrosine kinase inhibitors (TKIs), including lenvatinib, donafenib, apatinib, and sorafenib. Given that this study enrolled patients who progressed after an initial response to first-line targeted-immunotherapy, the second-line regimen in the control group continued tislelizumab immunotherapy while switching the TKI to regorafenib, an agent with second-line evidence.
• Clinically or pathologically confirmed unresectable primary hepatocellular carcinoma;
• Liver cancer patients with BCLC stage B or C;
• Not receiving systematic treatment before enrollment;
• Patients with acquired resistance who achieved disease control (DCR: CR, PR, or SD) following first-line targeted-immunotherapy but later experienced disease progression (PD);
• Child Pugh score ≤ 7 points;
• Subject must have at least 1 measurable target lesion examined by CT or MRI according to RECIST1.1 criteria;
• The Eastern Oncology Consortium (ECOG) Behavioral status score was 0 or 1.