Hepatocellular carcinoma (HCC) has a high risk of recurrence even after curative-intent resection or ablation. This remains one of the major challenges in HCC management, especially for patients with high-risk clinical or pathological features. Because atezolizumab plus bevacizumab is already used as a standard first-line treatment for unresectable HCC, the IMbrave050 trial tested whether the same combination could help reduce recurrence after curative-intent treatment.
The updated analysis was published in the Journal of Hepatology, Volume 84, Issue 6, June 2026.
Title: Updated data from IMbrave050: Adjuvant atezolizumab plus bevacizumab for high-risk hepatocellular carcinoma
Authors: Adam Yopp, Minshan Chen, Ann-Lii Cheng, Ahmed Kaseb, Masatoshi Kudo, Han Chu Lee, Edward Cha, Stephen Paul Hack, Qinshu Lian, Jessica Spahn, Chun Wu, Shukui Qin, Pierce Kah-Hoe Chow, and colleagues.
Why This Study Was Important
After surgery or ablation, many patients with HCC still experience recurrence. Early recurrence often reflects aggressive tumor biology or microscopic disease that was already present before treatment.
The rationale for IMbrave050 was based on the activity of atezolizumab plus bevacizumab in unresectable HCC. Atezolizumab targets PD-L1, while bevacizumab targets VEGF. Together, the combination may support antitumor immunity and modify the tumor microenvironment.
At the first interim analysis, IMbrave050 met its primary endpoint, showing improved recurrence-free survival. The updated analysis was performed to understand whether this early benefit remained with longer follow-up.
Study Design
IMbrave050 was a phase 3, randomized, open-label trial.
The study included patients with a first diagnosis of HCC who had undergone complete surgical resection or ablation within 4 to 12 weeks before randomization. Patients had Child-Pugh class A liver function, ECOG performance status 0 or 1, and a high risk of tumor recurrence.
A total of 668 patients were randomized:
- 334 received atezolizumab plus bevacizumab
- 334 underwent active surveillance
Patients in the treatment arm received atezolizumab 1,200 mg plus bevacizumab 15 mg/kg intravenously every 3 weeks for up to 12 months or 17 cycles. The primary endpoint was recurrence-free survival assessed by an independent review facility. Overall survival and safety were secondary endpoints.
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Updated Efficacy Results
The updated analysis was based on a data cut-off of May 3, 2024, with a median follow-up of 35.1 months. With longer follow-up, the early recurrence-free survival benefit was not sustained. Median recurrence-free survival was 33.2 months in the atezolizumab plus bevacizumab arm and 36.0 months in the active surveillance arm. The recurrence-free survival hazard ratio was 0.90.
Overall survival data remained immature. Median overall survival was not reached in either group. At the second interim analysis, the overall survival hazard ratio was 1.26.
The recurrence-free survival curves separated early but later converged and crossed around 2 years. This pattern suggests that adjuvant atezolizumab plus bevacizumab may have delayed recurrence in some patients during the first year, but the effect was not durable.
Exploratory Findings
Post hoc analyses were conducted specifically among patients who had undergone resection, to explore whether selected subgroups may have derived more benefit. Among patients beyond the up-to-7 criteria (a measure combining tumor size and number), median recurrence-free survival was 16.9 months with atezolizumab plus bevacizumab and 13.7 months with active surveillance (unstratified hazard ratio 0.84). In patients within the up-to-7 criteria, the recurrence-free survival hazard ratio was 1.01, indicating no benefit in that group.
Preoperative alpha-fetoprotein (AFP) levels were also evaluated retrospectively. Across the AFP-defined subgroups, AFP alone did not clearly identify patients more likely to benefit from adjuvant atezolizumab plus bevacizumab — a similar trend in recurrence-free survival was seen in both the low (≤20 ng/ml) and high (>400 ng/ml) AFP groups.
These exploratory findings suggest that future studies may require more refined risk models combining tumor burden, AFP, liver function, and biological markers. As post hoc, non-pre-specified analyses, they are hypothesis-generating only.
Recurrence and Post-Recurrence Treatment
Most recurrences were intrahepatic in both treatment arms (71% with atezolizumab plus bevacizumab vs. 65% with active surveillance), and extrahepatic recurrence rates were similar. Recurrent tumors were often small, solitary, unilobar intrahepatic lesions without macrovascular invasion. Among patients who had undergone resection and later developed recurrence, approximately one-third in each arm received treatment with curative intent, such as repeat resection or ablation.
Post-recurrence treatment patterns differed between arms. Locoregional therapy was more common after recurrence in the atezolizumab plus bevacizumab arm, while systemic therapy was more common in the surveillance arm — notably, 42% of patients in the surveillance arm received atezolizumab plus bevacizumab after recurrence. Overall, 99 patients (30%) in the surveillance arm crossed over to atezolizumab plus bevacizumab, which confounds interpretation of the overall survival data.
Safety
With longer follow-up, no new safety signals were reported. Among patients treated with atezolizumab plus bevacizumab, treatment-related adverse events occurred in 89%. Grade 3 or 4 treatment-related adverse events occurred in 36%, and grade 5 treatment-related events occurred in 1%. Common adverse events included proteinuria, hypertension, decreased platelet count, increased liver enzymes, hypothyroidism, arthralgia, pruritus, rash, and increased blood bilirubin.
Conclusion
With longer follow-up (median 35.1 months), adjuvant atezolizumab plus bevacizumab did not maintain the early recurrence-free survival benefit previously observed at the first interim analysis of IMbrave050. The recurrence-free survival hazard ratio was 0.90. Overall survival data remained immature, with an overall survival hazard ratio of 1.26 and a slight imbalance in deaths between arms (54 [16%] in the atezolizumab plus bevacizumab arm vs. 46 [14%] in the surveillance arm). This death imbalance, together with the reduced recurrence-free survival benefit, contributed to a negative shift in the benefit–risk assessment — particularly given the curative-intent nature of surgery or ablation in this population.
No new safety concerns were identified with longer follow-up. The updated benefit–risk profile does not support routine use of adjuvant atezolizumab plus bevacizumab for all patients with high-risk HCC after curative-intent resection or ablation. However, the data suggest the regimen may transiently delay recurrence in an as-yet-undefined subpopulation. IMbrave050 remains important for future HCC research because it highlights the need for better patient selection, longer follow-up, and more precise tools to identify patients who may benefit from perioperative or adjuvant therapy.
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