CIO 2023-13 IMbrave050: Phase 3 study of adjuvant atezolizumab + bevacizumab vs surveillance in hepatocellular carcinoma patients

Purpose: The risk of HCC recurrence after liver resection or ablation with curative intent is 70-80% within 5 years, indicating an unmet need for effective adjuvant therapies. Atezolizumab with bevacizumab is the standard of care for unresectable HCC based on the IMbrave150 study (Finn NEJM 2020, Cheng J Hepatol 2022). On the basis of the antitumor activity of atezo + bev and its capacity to modulate the tumor microenvironment, IMbrave050 was designed to evaluate the efficacy of adjuvant atezo + bev in delaying or preventing recurrence in patients with high-risk HCC.

Material and Methods: IMbrave050 (NCT04102098) enrolled pts with HCC at high risk of recurrence following resection or ablation. High-risk criteria were based on tumor burden, vascular invasion, and tumor differentiation. Pts were randomized to Arm A (atezo + bev) or Arm B (active surveillance). Stratification factors included geographic region and a composite factor encompassing the number of high-risk features, curative procedure, and use of optional adjuvant TACE (allowed for one cycle following resection). Pts in Arm A received atezo 1200mg + bev 15mg/kg IV q3w for a period of one year or 17 cycles. Pts in Arm B underwent active surveillance for one year and were eligible to crossover to atezo + bev following independent review facility confirmation of recurrence. The primary endpoint was IRF-assessed recurrence-free survival. Secondary efficacy endpoints included OS; investigator-assessed RFS; and time to extrahepatic spread and/or macrovascular invasion.

Results: The ITT population included 334 pts each in Arms A and B. Baseline demographics were balanced between arms. At interim analysis, with a median follow-up of 17.4 mo (cut off date: Oct 21 2022), the primary endpoint was met with an IRF-RFS HR of 0.72 (95% CI, 0.56, 0.93; P=0.0120). INV-RFS was similar (HR, 0.70; 95% CI, 0.54, 0.91). The safety of atezo + bev was consistent with the well-established safety profile of each therapeutic agent and with the underlying disease.

Conclusions: Atezo + bev is the first adjuvant regimen to demonstrate a statistically significant and clinically meaningful improvement in RFS vs active surveillance in pts at high risk of disease recurrence following resection or ablation. The benefit:risk profile of atezo + bev favors the use of this regimen as an adjuvant therapy and has potential to set a new standard of care in adjuvant HCC.