TALENTop: A multicenter, randomized study evaluating the efficacy and safety of hepatic resection for selected hepatocellular carcinoma with macrovascular invasion after initial atezolizumab plus bevacizumab treatment.

Abstract

TPS4175 Background: Hepatocellular carcinoma (HCC) patients with macrovascular invasion are consistently considered to be at an advanced stage of disease. The combination therapy of atezolizumab (atezo) plus bevacizumab (bev) has been the new standard-of-care for those patients. In patients responding to systemic therapy, hepatic resection may provide additional benefit. Here we propose a phase 3 study to investigate whether hepatic resection following atezo/bev can bring more benefits for HCC patients with macrovascular invasion when compared with atezo/bev alone. Methods: This is a multicenter, open-label, two-arm, randomized study designed to evaluate the efficacy and safety of surgical resection plus peri-operative atezo/bev compared with regular systemic atezo/bev (Q3W, every three weeks) in HCC patients with macrovascular invasion and without extrahepatic metastasis. Initially eligible patients have enrolled into induction phase, during which they receive 3 cycles of atezo/bev and 1 cycle of atezo alone as primary systemic therapy. Patients who are assessed as partial response or stable disease (RECIST v1.1 criteria) and considered suitable for R0 hepatic resection are randomized in a 1:1 ratio to either Arm A, hepatic resection with post-operative atezo/bev for 1 year (or until loss of clinical benefit or intolerable toxic effects), or Arm B, continuing atezo/bev for 1 year (or until loss of clinical benefit or intolerable toxic effects). The primary endpoint of this study is time-to treatment failure (TTF), defined as time from randomization to the first documented treatment failure (i.e., tumor recurrence or metastasis [Arm A], disease progression [Arm B] according to RECIST v1.1, or death from any cause). We hypothesize that hepatic surgery with peri-operative atezo/bev will improve the TTF from 5.8 months to 9.2 months, with the hazard ratio of 0.63. With 2-sided significance level of 0.05, the sample size for randomization will be 198. The study, registered with clinical trial ID of NCT04649489, started enrollment in Apr 2021. As of Jan 2022, 65 patients have been enrolled and 15 patients have been randomized. Research funding: Shanghai Roche Pharmaceuticals Ltd. Clinical trial information: NCT04649489.