Curative Therapy After Atezolizumab and Bevacizumab Treatment for Unresectable Hepatocellular Carcinoma

Curative Therapy After Atezolizumab and Bevacizumab Treatment for Unresectable Hepatocellular Carcinoma: A Multinational Retrospective Study

Combination immunotherapy is currently the standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Approximately 30 % of patients treated with atezolizumab plus bevacizumab (Atezo-Bev) achieve complete or partial tumor response. Some patients who reach a partial response experience enough tumor regression to undergo curative therapies and subsequently attain a disease-free state. However, whether the prognosis of patients who become disease-free after curative therapy equals that of patients who achieve complete response with Atezo-Bev alone is unclear. Likewise, it remains uncertain whether patients who achieve partial response with Atezo-Bev and later undergo curative therapy fare better than those who remain in partial response without further curative treatment. Therefore, we designed this multinational, multicenter, retrospective chart-review study to address these questions.

Planned Cohorts

• Curative-therapy cohort: Patients with unresectable HCC who achieve partial response to Atezo-Bev and subsequently receive curative therapy-surgical resection, radiofrequency ablation, or definitive radiotherapy-to achieve a disease-free state.
• Control cohort: Patients with unresectable HCC who achieve complete or partial response to Atezo-Bev but do not undergo subsequent curative therapy.

Methods and End-points Data will be collected from no more than 30 hospitals worldwide, targeting roughly 400 patients in the curative-therapy cohort and 1,200 patients in the control cohort. Medical-record review will gather baseline characteristics, disease status, liver function, Atezo-Bev treatment details, curative-therapy specifics, treatment responses, and survival outcomes. The primary objective is to compare recurrence-free survival between the two cohorts. This retrospective study will close data collection on 31 March 2025.

Inclusion Criteria:

1. Histologically or clinically (the presence of liver cirrhosis and typical HCC imaging findings by multi-phase CT or MRI) diagnosed HCC.
2. Received Atezo-Bev containing treatment as first-line systemic therapy for HCC
3. Patients with or without macrovascular invasion and main portal vein invasion before Atezo-Bev containing treatment can be enrolled
4. Patients with or without extrahepatic spread before Atezo-Bev containing treatment can be enrolled
5. Obtained CR or PR, according to RECIST version 1.1, to Atezo-Bev treatment

Exclusion Criteria:

1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
2. Received anti-CTLA4 antibodies simultaneously with Atezo-Bev Patients who received Atezo-Bev in combination with investigational drugs such as tiragolumab, relatlimab, and tocilizumab were allowed to enter the study.
3. Received locoregional therapy simultaneously with Atezo-Bev treatment, such as transarterial chemoembolization (TACE), hepatic arterial infusion of chemotherapy (HAIC), transarterial radioembolization, radiofrequency ablation, and microwave ablation before obtaining PR or not for curative intent