A multicenter phase II study on atezolizumab plus bevacizumab combination therapy in patients with unresectable hepatocellular carcinoma and Child–Pugh classification B cirrhosis: CHALLENGE trial

Introduction: Atezolizumab plus bevacizumab combination therapy (atezo + bev) has been successfully developed as a standard of care for patients with unresectable hepatocellular carcinoma (HCC) and Child–Pugh A; however, there is no established treatment for those with Child–Pugh B. This study aimed to evaluate the safety and efficacy of atezo + bev in patients with advanced HCC and Child–Pugh B. Methods: This multicenter, open-label, single-arm, phase II study enrolled patients with advanced HCC and a Child–Pugh score of 7 or 8 who had not received prior systemic therapy. Patients were administered atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was the frequency of serious adverse events (SAEs), assuming a threshold SAE of 68.5%. A binomial test with a one-sided significance level of 2.5% was employed for the primary analysis. Results: Among the 31 patients enrolled between December 2021 and April 2023, we set 30 eligible patients as the population for the safety and efficacy analyses. The frequency of SAEs was 23.3% (95% confidence interval [CI] 9.9–42.3, p <0.0001). Objective response rates according to RECIST v1.1 and the modified RECIST were 40.0% and 46.7%, respectively. The median progression-free and overall survival were 240 days (95% CI 176–526 days) and 470 days (95% CI 256–576 days), respectively. The mean ±SD Child–Pugh scores were 7.2 ± 0.4 at the start of treatment, maintained 7.0 ± 1.0 and 7.0 ±1.2 at the third and sixth cycles, respectively, and was 7.6 ± 1.7 at the end of treatment. Conclusion: The atezo + bev regimen can be safely administered with demonstrable antitumor effects in patients with unresectable HCC and a Child–Pugh score 7 or 8. Additional studies are warranted to confirm the usefulness of atezo + bev in this patient group.