The combination of atezolizumab plus bevacizumab (the “T+A” regimen) has established a new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the lack of long-term survival data and uncertainties regarding its effectiveness in complex real-world populations have remained major clinical concerns.At ESMO 2025, long-term follow-up data from the French CHIEF cohort (Carcinome HépatocellulaIrE en France) provided critical real-world evidence addressing these gaps. Oncology Frontier invited Professor Manon Allaire, Head of the Liver Tumor Unit at Pitié-Salpêtrière Hospital, Paris, for an in-depth interpretation.
Professor Allaire emphasized that this study not only demonstrated the durable and powerful real-world efficacy of the T+A regimen—with a median overall survival (mOS) of 22.8 months—but also provided strong support for earlier use of systemic therapy in selected Child–Pugh B patients and even some BCLC-B patients. She further stressed that improving HCC outcomes requires breaking away from the paradigm of “treating the tumor while ignoring the liver,” advocating instead for comprehensive, longitudinal management that includes portal hypertension and other cirrhosis-related complications, as well as precision strategies for patients with oligoprogression and favorable biology.
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Oncology Frontier:** The 42-month long-term real-world follow-up study of atezolizumab plus bevacizumab as first-line therapy for advanced HCC has yielded remarkable results. How do you think these findings will specifically influence current clinical decision-making for patients with advanced HCC?
Professor Manon Allaire
At this year’s ESMO Congress, long-term follow-up data were presented for patients with unresectable HCC treated with the T+A regimen as first-line therapy. These real-world data are of critical importance. As we know, the IMbrave150 trial unfortunately did not provide long-term survival outcomes, and our study helps fill this important gap, offering substantial clinical reference value.
In addition, the CHIEF cohort has particular relevance to clinical practice in France. In IMbrave150, most enrolled patients had viral hepatitis–related liver disease, which does not reflect the epidemiological profile in France, where the majority of patients have alcohol-related cirrhosis. The CHIEF cohort was therefore designed to evaluate the efficacy and safety of the T+A regimen specifically in this population.
The results were highly encouraging. The median overall survival reached 22.8 months, representing one of the best outcomes reported to date in real-world studies. Moreover, the 42-month overall survival rate remained as high as 44%, providing compelling evidence of the long-term benefit of this combination therapy in complex real-world patient populations.
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Oncology Frontier:** Your results showed significant differences in overall survival and progression-free survival across patients with different BCLC stages, Child–Pugh classes, and ALBI grades. Could you elaborate on these differences and their broader clinical implications?
Professor Manon Allaire
This cohort indeed had distinctive clinical characteristics. Notably, 21% of patients were classified as Child–Pugh B. Updated analyses showed that although survival in Child–Pugh B patients was inferior to that of Child–Pugh A patients, their median survival still reached approximately 10 months, which is quite encouraging.
These findings suggest that it may be reasonable to expand the indication of the T+A regimen to carefully selected Child–Pugh B patients, whereas most centers currently restrict its use to Child–Pugh A patients.
A similar trend was observed with ALBI grading. The cohort included a substantial proportion of ALBI grade 2 patients and some ALBI grade 3 patients. Survival was significantly poorer in ALBI grade 3 patients, indicating that this therapy may not be suitable for individuals with very limited hepatic reserve.
Regarding BCLC-B patients, who accounted for approximately 30% of the 880-patient cohort, their overall survival was relatively favorable, as expected. Importantly, these findings prompt a reassessment of treatment strategies. For some intermediate-stage HCC patients, systemic therapy should be considered earlier, rather than repeated transarterial chemoembolization (TACE).
This is particularly relevant in France, where many patients have alcohol-related cirrhosis. Compared with Asian populations, these patients often have poorer liver function and a higher risk of decompensation, making clinicians more cautious about TACE and more inclined to prioritize systemic therapy.
Within the BCLC-B subgroup in our cohort, approximately one-third were Child–Pugh B patients (for whom TACE is not recommended in France), and another one-third had progressed after local therapies. These “new” patient populations—often excluded from large phase III trials in advanced HCC—achieved excellent outcomes when systemic therapy was used as first-line treatment.
Therefore, in carefully selected BCLC-B patients, systemic therapy should be actively considered as a first-line option, in line with the evolving direction of the BCLC treatment algorithm.
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Oncology Frontier:** Multivariate analysis identified factors such as esophageal varices, ascites, and ALBI grade 2 as being associated with higher mortality. How should clinicians integrate these prognostic factors into real-world practice to better individualize treatment and improve outcomes?
Professor Manon Allaire
These findings have very strong clinical implications. They clearly show that patients with portal hypertension or impaired liver function have significantly higher mortality. This underscores the need for a fundamental shift in clinical mindset: when managing HCC, clinicians must not focus solely on the tumor.
The vast majority of HCC patients have underlying cirrhosis, which must be addressed as part of comprehensive, longitudinal care. For example, screening for portal hypertension is essential. In France, we recommend endoscopic evaluation for all patients. If clinically significant portal hypertension (CSPH) is identified, non-selective beta-blockers are prescribed prophylactically to reduce the risk of hepatic decompensation.
At the same time, it is crucial to identify and manage the underlying liver disease, including antiviral therapy for hepatitis B or C, as well as control of metabolic syndrome and alcohol consumption.
Ultimately, this study provides strong evidence that effective HCC management requires not only systemic antitumor therapy, but also comprehensive management of cirrhosis, including proactive screening for portal hypertension and timely etiologic treatment. This integrated approach is fundamental to improving patient prognosis.
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Oncology Frontier:** Based on these findings, what do you see as the most important research directions in advanced HCC, and where should future efforts be focused?
Professor Manon Allaire
One of the most important observations from this study is that approximately 30% of patients achieved durable responses, which is a crucial finding. Future research should therefore focus on identifying these patients more precisely through translational approaches, such as tissue biopsies or blood-based biomarkers, to better define populations that derive the greatest benefit from immunotherapy.
Another key area of investigation is the management of disease progression. For instance, when patients receiving the T+A regimen develop oligoprogression—progression in a single lesion—the clinical dilemma is whether to discontinue therapy and switch to the next line, or whether to follow the approach commonly used in Asia by combining continued systemic therapy with local treatment.
In France and across Europe, there is growing interest in exploring this strategy of maintaining systemic therapy while adding local interventions, with the goal of further extending survival in selected patients.
