Atezolizumab-bevacizumab provides optimal balance between survival, QoL benefits in HCC

A network meta-analysis (NMA) reports that the combination regimen comprising atezolizumab and bevacizumab appears to be better than other first-line systemic therapeutic alternatives for advanced hepatocellular carcinoma (HCC) in terms of providing a balance between overall survival (OS) benefit and quality of life (QoL) preservation.

“OS remains the primary endpoint in the treatment of unresectable or advanced HCC, but health-related QoL (HRQoL) is a crucial complementary outcome in the face of widening treatment options that has not been comprehensively compared across available treatments,” noted presenting author Dr Ciro Celsa from the Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo in Italy, at EASL 2025.

Several immune checkpoint inhibitor (ICI) combinations have been reported to be superior to tyrosine kinase inhibitors (TKIs); however, there are no comparative analyses substantiating their HRQoL impact.

Hence, the investigators sought to compare the effects of various first-line treatments for advanced HCC on HRQoL and integrate treatment-induced survival benefit with impact on HRQoL. [EASL 2025, abstract FRI-089-YI]

A systematic literature search of databases was conducted to identify all phase III randomized trials published through November 2024. Trials included are those that compared TKI monotherapy with ICI-based regimens in the first-line treatment of unresectable/advanced HCC and reported time to deterioration of HRQoL scores. A frequentist NMA was done using sorafenib as the comparator.

The NMA included ten studies (n=7,268) comprising patients who have been treated with monotherapies such as durvalumab, lenvatinib, nivolumab, sorafenib, and tislelizumab, as well as combination regimens comprising atezolizumab and bevacizumab, atezolizumab and cabozantinib, camrelizumab and apatinib, durvalumab and tremelimumab, nivolumab and ipilimumab, lenvatinib and pembrolizumab, and sintilimab and IBI305.

The atezolizumab plus bevacizumab combination demonstrated the highest probability of reducing the risk of deterioration of global health status/quality of life (GHS/QoL; 85 percent), abdominal swelling (95 percent), jaundice (89 percent), and pain (86 percent).

Tislelizumab showed the highest probability of reducing the risk of deterioration of physical functioning (96 percent) and fatigue assessed by the EORTC* Quality of Life Questionnaire (QLQ)-C30 and QLQ-HCC18 (98 percent and 86 percent, respectively).

When GHS/QoL and OS were combined, the atezolizumab plus bevacizumab combo regimen outdid the other treatments, yielding the best minimum distance criterion (MDC; 0.19). Sintilimab plus IBI305 (MDC, 0.37), lenvatinib plus pembrolizumab (MDC, 0.56), and durvalumab plus tremelimumab (MDC, 0.64) took the second, third, and fourth spots, respectively.

“[We used the MDC approach] to combine HRQoL and OS by minimizing the statistical distance between observed results and a theoretical optimal point where both outcomes are maximized. A lower MDC corresponds to an improved net benefit across both HRQoL and OS,” explained Celsa and colleagues.

Furthermore, the atezolizumab plus bevacizumab combo consistently outperformed the other treatment alternatives when looking at the MDCs for the other EORTC QLQ-C30 (0.26 for fatigue and 0.20 for physical functioning) and QLQ HCC18 (0.16, 0.19, 0.14, and 0.19 for jaundice, pain, abdominal swelling, and fatigue, respectively) domains. For the other regimens, MDCs ranged between 0.23 (sintilimab plus IBI305) and 1.37 (sorafenib), both for the QLQ HCC18 – fatigue domain.

Takeaways

“[This NMA shows that] atezolizumab plus bevacizumab was associated with the highest magnitude in reducing the risk of deterioration of most HRQoL domains compared with other systemic therapies,” the investigators said.

Moreover, the integrated assessment of OS with HRQoL as evaluated by MDC suggests that atezolizumab plus bevacizumab provides the best balance between QoL preservation and OS benefit compared with other systemic therapy options in unresectable/advanced HCC, they added.