Low-Dose Bevacizumab Maintains Efficacy With Reduced Adverse Events in Liver Cancer.

BACKGROUND

Atezolizumab plus bevacizumab (Atezo/Bev) is the standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). In the IMbrave150 trial, bevacizumab-related adverse events (AEs) frequently required dose interruption or discontinuation, raising concerns regarding optimal dosing. The effect of initiating therapy with low-dose bevacizumab remains uncertain.

METHODS

We retrospectively analysed 307 uHCC patients who received Atezo/Bev as first-line therapy between 2020 and 2025. Patients were categorised into standard-dose (15 mg/kg) or low-dose (5-7.5 mg/kg) groups, with low-dose allocation determined solely by a patient support programme, not by clinical discretion. After 1:1 propensity score matching, 122 patients in each group were compared. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety.

RESULTS

Efficacy outcomes were similar between low- and standard-dose groups: ORR (37.7% vs. 32.8%, p = 0.421), DCR (65.6% vs. 64.8%, p = 0.789), median PFS (7.3 vs. 8.1 months, p = 0.460) and OS (24.6 vs. 20.7 months, p = 0.689). The incidence of severe AEs did not differ, but low-dose bevacizumab significantly reduced low-grade toxicities, including proteinuria (28.7% vs. 40.2%, p = 0.045), rash (10.7% vs. 23.8%, p = 0.007), thrombocytopenia (13.9% vs. 20.5%, p = 0.049) and gastrointestinal bleeding (1.6% vs. 4.9%, p = 0.044). Moreover, post-progression overall survival did not significantly differ between prior standard- and low-dose bevacizumab patients (11.2 vs. 9.4 months, p = 0.700).

CONCLUSIONS

In this real-world cohort, low-dose bevacizumab preserved antitumor efficacy while reducing key AEs, suggesting that a dose de-escalation strategy may improve tolerability without an early compromise in survival outcomes, although longer follow-up is needed to confirm that long-term efficacy remains comparable.