CHALLENGE Trial Final Results: Atezolizumab Plus Bevacizumab in Advanced HCC With Child-Pugh Class B Cirrhosis

The CHALLENGE trial, a multicenter, open-label, phase II study, has provided important insights into the safety and efficacy of atezolizumab plus bevacizumab (atezo+bev) combination therapy for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh class B cirrhosis. This patient population represents a significant treatment challenge due to compromised liver function and the limited efficacy of available therapies. The results were presented at the American Society of Clinical Oncology 2025 Gastrointestinal Cancers Symposium by Masafumi Ikeda, of National Cancer Center Hospital East in Japan.

Study Design and Patient Population
Conducted across multiple centers, the CHALLENGE trial enrolled 31 patients with unresectable HCC and a Child-Pugh score of 7 or 8. Eligible patients had not received prior systemic therapy. Most participants (80.6%) had a Child-Pugh score of 7, and the remaining 19.4% had a score of 8. Approximately 45.2% were classified as having Barcelona Clinic Liver Cancer stage C disease. Treatment consisted of atezolizumab, 1200 mg, plus bevacizumab, 15 mg/kg, administered every three weeks.

The trial’s primary endpoint was the frequency of severe adverse events (SAEs); secondary endpoints included objective response rate (ORR), progression-free survival (PFS), time to progression (TTP), overall survival (OS), and the frequency of adverse events (AEs).

Key Findings
At a median follow-up of 517 days, the results demonstrated both tolerability and antitumor activity of atezo+bev in this challenging cohort. SAEs were reported in 30% of patients (95% CI, 14.7-49.4), with the most frequent grade ≥3 SAEs being increased blood bilirubin and proteinuria (n=3 each), hypoalbuminemia (n=2), and hypertension (n=2). Severe liver-related AEs occurred in seven patients (23.3%), including esophageal varices hemorrhage (n=2). Immune-related grade ≥3 AEs were rare but included mucositis and malaise (n=1 each).

The ORR was 40% based on RECIST 1.1 and 46.7% based on modified RECIST criteria, reflecting promising antitumor activity. Median PFS and TTP were both 240 days (95% CI, 176-526), and median OS was 470 days (95% CI, 256-576).

These results suggest that atezo+bev offers a viable treatment option for patients with advanced HCC and moderate hepatic impairment, demonstrating significant antitumor efficacy with manageable safety risks. The ORR of approximately 40% aligns with favorable outcomes seen in less impaired populations, underscoring the potential of this regimen for patients with compromised liver function.

The occurrence of severe liver-related AEs, such as esophageal varices hemorrhage, emphasizes the need for close monitoring and a multidisciplinary approach to care. The study also highlights the stability of Child-Pugh scores during initial treatment cycles, suggesting that atezo+bev does not exacerbate hepatic decompensation in the short term.

Future Directions
The authors note that additional studies are needed to validate the efficacy and safety of atezo+bev in this subgroup. Future research should focus on refining patient selection criteria and optimizing management strategies for liver-related and immune-related adverse events.