Transarterial Radioembolization Versus Atezolizumab-Bevacizumab in Unresectable Hepatocellular Carcinoma: A Matching-Adjusted Indirect Comparison of Time to Deterioration in Quality of Life

Plain Language Summary For patients with hepatocellular carcinoma, as well as physicians treating hepatocellular carcinoma, the quality of life that different treatments can offer represents an increasingly important aspect to consider when choosing treatments. Transarterial radioembolization and atezolizumab-bevacizumab are two potential treatments for advanced and unresectable hepatocellular carcinoma, but no clinical trials have directly compared the outcomes of these two therapeutic options. With the data available (patient-level data from a clinical trial of transarterial radioembolization using SIR-Spheres(R) Y-90 resin microspheres [SIR-Spheres] versus sorafenib and data from a trial of atezolizumab-bevacizumab versus sorafenib from the literature), this study indirectly compared the time to deterioration of quality of life (i.e., how long quality of life is maintained) after treatment with transarterial radioembolization and atezolizumab-bevacizumab. The study showed that quality of life may be preserved over a similar time period with transarterial radioembolization using SIR-Spheres and atezolizumab-bevacizumab; also, both transarterial radioembolization using SIR-Spheres and atezolizumab-bevacizumab seem to maintain patients' quality of life over a longer period of time compared with sorafenib. These results are expected to enrich the existing evidence on which patients and physicians can base their decisions, allowing them to choose the most appropriate treatment by assessing the treatments' characteristics as a whole. Introduction Given the relatively short life expectancy of patients with hepatocellular carcinoma (HCC), quality of life (QOL) plays a significant role in treatment selection. This analysis aimed to compare time to deterioration (TTD) in QOL with transarterial radioembolization (TARE) and atezolizumab-bevacizumab, as well as sorafenib, in advanced and unresectable HCC. Methods Patient-level data from SARAH (TARE using SIR-Spheres(R) Y-90 resin microspheres [SIR-Spheres] versus sorafenib) and aggregate data from IMbrave150 (atezolizumab-bevacizumab versus sorafenib) randomized controlled trials were used to conduct an anchored matching-adjusted indirect comparison (MAIC). Patients with a Child-Pugh score B in SARAH were excluded to align with exclusion criteria in IMbrave150. To identify potential effect modifiers for adjustment, the literature was searched and multivariate Cox proportional hazards models were implemented using SARAH data. Patients from SARAH were then weighted to balance with baseline characteristics from IMbrave150. Median TTD in QOL and hazard ratios (HRs) were calculated. Results Four potential effect modifiers were identified and used for adjustment: cause of disease (viral/non-viral), macrovascular invasion, Eastern Cooperative Oncology Group performance score, and alpha-fetoprotein level. The MAIC included 217 patients from SARAH (TARE = 94; sorafenib = 123). Median TTD in QOL was 11.23 and 8.64 months for atezolizumab-bevacizumab and TARE, respectively (HR = 1.06; 95% confidence interval [CI] 0.75-1.50; p = 0.725). A sensitivity analysis was conducted adjusting for cause of disease defined as hepatitis B/hepatitis C/non-viral: median TTD in QOL was higher for TARE compared with atezolizumab-bevacizumab (19.88 vs 11.23 months; HR = 0.66; 95% CI 0.36-1.19; p = 0.163). Sorafenib resulted in the shortest TTD in QOL, with statistically significant differences in both base case and sensitivity analyses. Conclusion TARE using SIR-Spheres may achieve similar TTD in QOL compared with atezolizumab-bevacizumab, as the analyses found no statistically significant differences between these two interventions. Both TARE using SIR-Spheres and atezolizumab-bevacizumab seem to be more efficacious than sorafenib in maintaining QOL.