A comprehensive network meta-analysis published in JAMA Oncology has identified atezolizumab plus bevacizumab as the optimal first-line systemic therapy for patients with unresectable or advanced hepatocellular carcinoma (HCC), offering superior balance between survival benefit and quality-of-life preservation compared to other available treatments.
The study, led by Celsa et al, analyzed data from nine phase III randomized clinical trials involving 6,425 patients to address a critical gap in understanding patient-centered outcomes across different immunotherapy-based treatment options. "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 noted.
Comprehensive Analysis of Treatment Options
The research team conducted a systematic literature search across MEDLINE, CENTRAL, and Scopus databases from inception through November 2024, supplemented by manual reviews of reference lists and conference abstracts from 2020 to 2024. The analysis included trials comparing tyrosine kinase inhibitor monotherapy with immune checkpoint inhibitor-based therapies in first-line advanced HCC that reported health-related quality-of-life deterioration data.
Using sorafenib as the comparator, the investigators performed a Bayesian network meta-analysis to evaluate time to deterioration of health-related quality-of-life scores across seven different quality-of-life domains among various treatment regimens.
Superior Quality-of-Life Outcomes
Based on surface under the cumulative ranking calculations, atezolizumab plus bevacizumab demonstrated remarkable superiority across multiple quality-of-life parameters. The combination showed the greatest likelihood of reducing deterioration in global health status (85%), abdominal swelling (95%), jaundice (89%), and pain (86%). Notably, tislelizumab ranked highest for physical functioning (96%) and fatigue management.
The analysis revealed that when integrating quality of life with overall survival outcomes, atezolizumab plus bevacizumab significantly outperformed all other treatments across all measured domains, establishing it as the most comprehensive therapeutic option for advanced HCC patients.
Paradigm Shift in Treatment Evaluation
The study's findings underscore a fundamental shift toward patient-centered care in HCC management. "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," the investigators explained.
This research addresses the critical need for comprehensive treatment evaluation that extends beyond traditional survival metrics to encompass the patient experience throughout therapy. The integration of quality-of-life measures with survival outcomes provides clinicians with more nuanced data to guide treatment decisions.
Clinical Implications and Future Directions
The investigators emphasized the transformative potential of their findings for clinical practice and future research design. "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," they concluded.
This approach represents a significant advancement in HCC treatment evaluation, moving beyond the traditional focus on survival endpoints to embrace a more holistic assessment of therapeutic benefit that considers the patient's overall well-being and functional status during treatment.
The study's methodology, involving two independent reviewers for study selection and data extraction with risk of bias assessment using the Cochrane Collaboration tool, ensures robust and reliable findings that can inform clinical decision-making and future research directions in advanced HCC management.
