Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
REPLACEMENT trial in progress: Combination therapy with atezolizumab plus bevacizumab for TACE unsuitable patients with beyond up-to-seven criteria in intermediate stage hepatocellular carcinoma: A phase II study.
Background: Transarterial chemoembolization (TACE) had been developed as a standard of care in patients with intermediate-stage HCC at a time when systemic therapy was not available. This stage includes a certain TACE-unsuitable subpopulation, such as beyond up-to-seven criteria. Recently, the American Association for the Study of Liver Diseases and Asia-Pacific Primary Liver Cancer Expert Meeting have recommended systemic therapy for those patients to achieve overall survival (OS) beyond 2 years without impaired liver function in their consensus guideline. However, there is not enough data on systemic therapy for this population. Atezolizumab (Atezo), anti-PD-L1 antibody, plus Bevacizumab (Bev), anti-VEGF antibody, combination therapy has been shown to significantly improve OS, progression-free survival (PFS), and overall response rate (ORR) against sorafenib, which is a standard of care in unresectable HCC according to a phase III randomized controlled trial, IMbrave150. Therefore, we investigate the efficacy and safety of Atezo+Bev combination therapy in patients with HCC beyond up-to-seven criteria in this trial. Methods: REPLACEMENT trial is a multicenter, single-arm phase II study of Atezo+Bev combination therapy. Key eligibility criteria are age ≥20 years, ECOG performance status 0-1, Child-Pugh A, no vascular invasion, no extrahepatic metastasis, beyond up-to-seven criteria, and patients who have received neither systemic therapy nor TACE. Patients will be administrated Atezo 1200 mg/body + Bev 15 mg/kg once every 3 weeks. The primary endpoint is PFS per modified RECIST (mRECIST). The secondary endpoints include PFS, ORR, duration of response (DOR) per mRECIST; PFS, ORR, DOR per RECIST ver.1.1; OS and safety including change of liver function based on albumin-bilirubin (ALBI) score until disease progression. A total of 60 events are necessary to investigate the hypothesis that a target point estimation of PFS rate at 6 months (null population: 55%, alternative population: 73%). The estimated sample size is, therefore, 70 patients. In addition, the results of the Atezo+Bev therapy in this arm will be compared with those in approximately 600 TACE treated consecutive patients with intermediate-stage HCC, using the propensity score matching method, as an exploratory analysis of a possible replacement of TACE by the Atezo+Bev therapy. Patients’ enrollment had already started in December 2020, and 12 patients were enrolled as of 16th February ’21. Clinical trial information: jRCTs071200051.