Adding Tecentriq (atezolizumab) to Tecentriq plus Avastin (bevacizumab) and tiragolumab treatment did not show an added benefit in patients with untreated locally advanced or metastatic hepatocellular carcinoma, according to data from a phase 3 study presented during the 2025 ESMO Congress. The co-primary end point of investigator-assessed progression-free survival was missed.
Patients treated with placebo plus Tecentriq and Avastin (338 patients) had an investigator-assessed median progression-free survival of 8.2 months versus 8.3 months in patients treated with tiragolumab plus Tecentriq plus Avastin. Overall survival data remain immature and are not anticipated to reach statistical significance, according to study authors.
“These data, now from a double-blind, placebo-controlled study of over 600 patients, confirm the activity of Tecentriq plus Avastin in the management of this population as well as the safety, and moving forward, we will hopefully learn a lot from the study on how to best decide to move forward in advancing care for our patients with hepatocellular carcinoma,” study author and presenter, Dr. Richard S. Finn, stated. Dr. Finn is a professor of medicine at the David Geffen School of Medicine, University of California, Los Angeles, and director of the UCLA Liver Cancer Program.
Trial Design and Baseline Characteristics
The study is a double-blind, placebo-controlled, randomized global trial that enrolled 669 patients between September 14, 2023, and September 23, 2024. Eligible patients were 18 years or older with unresectable locally advanced or metastatic hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and Child-Pugh A liver function.
Glossary
Overall survival (OS): time from treatment start until death from any cause.
Objective response rate (ORR): percentage of patients whose cancer shrinks or disappears after treatment.
Complete response (CR): disappearance of all signs of cancer in response to treatment.
Partial response (PR): significant reduction, but not disappearance, of cancer after treatment.
Duration of response (DOR): length of time a treatment keeps cancer under control after it first responds.
Stable disease (SD): cancer that neither shrinks significantly nor grows.
Progressive disease (PD): cancer that grows or spreads while on treatment.
Disease control rate (DCR): percentage of patients whose cancer shrinks, disappears, or remains stable after treatment.
Patients were excluded if they had received prior systemic therapy for advanced disease or experienced recurrence within 26 months of completing adjuvant treatment. Participants were randomized one-to-one to receive either tiragolumab six hundred milligrams plus Tecentriq one thousand two hundred milligrams plus Avastin fifteen milligrams per kilogram intravenously every three weeks or placebo plus Tecentriq one thousand two hundred milligrams and Avastin fifteen milligrams per kilogram intravenously every three weeks.
Treatment continued until loss of clinical benefit or unacceptable toxicity, and crossover was not allowed. Imaging assessments were performed every six weeks, with a one-week margin. Stratification factors included geographic region (Asia and Africa versus the rest of the world including Japan), macroscopic vascular invasion and/or extrahepatic spread, baseline alpha-fetoprotein level (≥400 nanograms per milliliter versus <400 nanograms per milliliter), and hepatocellular carcinoma etiology (viral versus non-viral).
The study’s primary end points were investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1 criteria and overall survival. Key secondary end points included objective response rate, duration of response, progression-free survival and overall survival rates at select time points, safety, and patient-reported outcomes.
Baseline characteristics were generally well-balanced between the tiragolumab (331 patients) and the placebo (338 patients) arms. The median age for all patients (669 patients) was 44.5 years, with 82% aged 65 years or older. The majority were male (87.6% in both arms).
The most common geographic region was Asia/Asian Pacific/Australia (tiragolumab, 52%; placebo, 48.1%), followed by Europe and Middle East/North America (18.7%; 17.5%). Hepatitis B was the most frequent hepatocellular carcinoma etiology (65.6%; 59.8%), while 76.1% of all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The majority had Barcelona Clinic Liver Cancer stage B or C disease (75.9% overall) and a Child-Pugh score of A5 or A6 (63.5% overall).
