Real-world outcomes of combination immunotherapy in patients with Child–Pugh class B hepatocellular carcinoma.

556 Background: Systemic therapy for hepatocellular carcinoma (HCC) is primarily recommended for patients with preserved liver function (Child–Pugh A, CP-A). Evidence in Child–Pugh B (CP-B) remains scarce. We evaluated real-world outcomes of atezolizumab plus bevacizumab (Atezo+Bev) and durvalumab plus tremelimumab (Dur+Tre) in patients with CP-B. Methods: We retrospectively analyzed 222 patients with unresectable HCC treated with Atezo+Bev or Dur+Tre. Tumor response was assessed by RECIST v1.1 and safety by CTCAE v5.0. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment discontinuation, and subsequent therapy. Results: With Atezo+Bev, median PFS was 6.0 months in CP-A (n=149) and 7.1 months in CP-B (n=23), and median OS was 23.8 vs 8.5 months. With Dur+Tre, median PFS was 2.8 months in CP-A (n=38) and 1.8 months in CP-B (n=12), with OS not reached in CP-A vs 3.9 months in CP-B. In CP-B patients, ORR was 10.5% with Atezo+Bev and 0% with Dur+Tre; DCR was 63.2% and 40.0%, respectively. PFS in CP-B patients was comparable to CP-A, but OS was shorter. Transition to subsequent therapy was less frequent in CP-B than CP-A with Atezo+Bev (47.6% vs 77.6%, p<0.01), while no significant difference was observed with Dur+Tre (50.0% vs 81.2%, p=0.09). Treatment discontinuation rates in CP-B were similar (Atezo+Bev 28.6% vs Dur+Tre 30.0%), but the causes differed: anti-VEGF (11.1%) and portal hypertension–related events (8.3%) with Atezo+Bev, versus predominantly immune-related events with Dur+Tre (90%). Conclusions: In real-world practice, PFS was not significantly impaired in CP-B compared with CP-A, but OS was shorter, and access to subsequent therapy was limited, particularly with Atezo+Bev. While overall discontinuation rates were similar between regimens, the underlying causes differed, reflecting distinct toxicity profiles. These findings underscore the need for tailored management strategies in patients with impaired liver function.