A network meta-analysis reported in JAMA Oncology found that among first-line systemic therapy options, immunotherapy-based combinations—particularly atezolizumab plus bevacizumab—offered the most favorable therapeutic balance between survival benefit and quality-of-life preservation in unresectable or advanced hepatocellular carcinoma. Celsa et al emphasized the value of this integrated approach in supporting more patient-centered treatment decision-making.
“Patient-reported outcomes have emerged as crucial endpoints in oncology trials, providing patient-centric assessment of treatment effects with prognostic value beyond traditional clinical measures,” the investigators commented. “Despite widening in systemic therapy options, no study had ever compared patient-reported outcomes and survival across immune checkpoint inhibitor combinations, a factor that limits a full understanding of the net benefit associated with each of the available treatments with positive phase III readouts.”
Study Details
The investigators conducted a systematic literature search to identify eligible phase III randomized clinical trials in the MEDLINE, CENTRAL, and Scopus databases published between inception and November 2024, as well as manual reviews of reference lists and conference abstracts presented between 2020 and 2024. Those comparing tyrosine kinase inhibitor monotherapy with immune checkpoint inhibitor−based therapies in first-line advanced hepatocellular carcinoma and reporting health-related quality-of-life deterioration were included; a total of nine trials, involving seven health-related quality-of-life items and 6,425 patients, met these criteria.
Two independent reviewers performed study selection and data extraction. The risk of bias was assessed using the Cochrane Collaboration tool. Using sorafenib as the comparator, the investigators performed a Bayesian network meta-analysis to compare time to deterioration of health-related quality-of-life scores among different treatments.
Key Findings
Based on surface under the cumulative ranking calculations, atezolizumab plus bevacizumab demonstrated the greatest likelihood of reducing deterioration in most quality-of-life domains, including global health status (85%), abdominal swelling (95%), jaundice (89%), and pain (86%); tislelizumab was found to rank highest for physical functioning (96%) and fatigue. When integrating quality of life with overall survival, according to the investigators, atezolizumab plus bevacizumab significantly outperformed all other treatments across all measured domains.
“Composite endpoints combining survival and quality-of-life outcomes should be considered as a novel and more patient-centric approach to define the extent of clinical benefit in routine practice and in clinical trials of novel agents for the treatment of hepatocellular carcinoma,” the investigators concluded.
David James Pinato, MD, MRes, PhD, of Imperial College London, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was funded by the European Society of Medical Oncology, UK National Institute for Health Research Imperial Biomedical Research Centre, European Association for the Study of the Liver, Cancer Research UK, European Union−NextGenerationEU (through the Italian Ministry of University and Research), Cancer Treatment and Research Trust, Foundation for Liver Research, and Imperial Experimental Cancer Medicine Centre. For full disclosures of the study authors, visit jamanetwork.com.
