Which First-line Treatment Is Best?

TOPLINE: 

In a meta-analysis assessing first-line treatment options for advanced hepatocellular carcinoma (HCC), atezolizumab plus bevacizumab demonstrated the highest overall probability of delaying deterioration across key quality-of-life (QoL) domains and outperformed other treatment options when integrating health-related QoL with overall survival benefits.

METHODOLOGY:

• The therapeutic landscape for advanced HCC has “evolved dramatically since 2018,” the authors explained. Current first-line options include combinations of immune checkpoint inhibitors (ICIs), such as atezolizumab plus bevacizumab and durvalumab plus tremelimumab, as well as other combinations and monotherapy. However, there’s limited evidence comparing these options in terms of survival benefit and QoL.
• Researchers performed a network meta-analysis of nine phase 3 randomized clinical trials involving 6425 patients. These trials compared a range of treatment options, including tyrosine kinase inhibitor and ICI monotherapy as well as ICI-based combination therapies.
• All studies had two treatment arms, except one trial that had three. The control arm received sorafenib in seven studies and lenvatinib in one study. Other therapies assessed included tislelizumab, atezolizumab plus bevacizumab, sintilimab plus IBI305, and durvalumab plus tremelimumab.
• Researchers used questionnaires to assess time to deterioration of six health-related QoL domains: global health status, physical functioning, fatigue, jaundice, pain, and abdominal swelling.
• Surface under the cumulative ranking (SUCRA) scores were calculated for each domain. SUCRA represents the probability that a given treatment is the best among all evaluated treatments, where 0 indicates a treatment is the worst and 1 indicates it’s the best.

TAKEAWAY:

• Atezolizumab plus bevacizumab had the highest probability of delaying deterioration across four key domains: global health status and QoL (SUCRA, 0.85 ; hazard ratio [HR], 0.63 ), abdominal swelling (SUCRA, 0.950; HR, 0.57 ), jaundice (SUCRA, 0.895; HR, 0.77) , and pain (SUCRA, 0.861; HR, 0.65). The combination was slightly edged out by sintilimab plus IBI305 for best likely overall survival benefit (SUCRA, 0.873 vs 0.892, respectively).
• Sintilimab plus IBI305 ranked second for pain (SUCRA, 0.739; HR, 0.73) and third for abdominal swelling (SUCRA, 0.689; HR, 0.78), fatigue (SUCRA, 0.800; HR, 0.63), and jaundice (SUCRA, 0.582; HR, 0.96).
• Sorafenib monotherapy ranked lowest across domains of pain, fatigue, physical functioning, and global health status. And tislelizumab demonstrated superior preservation of physical functioning and fatigue, offering an alternative specifically for QoL.
• When researchers integrated HR-QoL with overall survival, atezolizumab plus bevacizumab consistently outperformed all other regimens, while lenvatinib and sorafenib monotherapy ranked at the bottom.

IN PRACTICE:

“This network meta-analysis provides robust evidence that immunotherapy-based combinations, particularly atezolizumab plus bevacizumab, offer the most favorable balance between survival benefit and QoL preservation in advanced HCC,” the authors wrote. 

SOURCE:

The study, led by David James Pinato, MD, MRes, PhD, Imperial College London Hammersmith Campus, London, England, was published online in JAMA Oncology.

LIMITATIONS:

The analysis relied on aggregate data, which limited patient-level insights. Heterogeneity in health-related QoL assessment tools and definitions of deterioration across studies affected comparability. The composite endpoint assumed independence between survival and QoL. Additionally, HR-QoL data were unavailable for some regimens due to inconsistent reporting.

DISCLOSURES:

The study received funding from multiple sources, including the European Society for Medical Oncology, UK National Institute for Health and Care Research Imperial Biomedical Research Centre, European Association for the Study of the Liver, Cancer Research UK, and the European Union’s NextGenerationEU. Several authors reported receiving consulting fees or personal fees and having other ties with various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.