Comparison of Atezolizumab/Bevacizumab Versus Durvalumab/Tremelimumab (STRIDE) Protocols in Locally Advanced or Metastatic Hepatocellular Carcinoma Among Patients in Sohag

Hepatocellular carcinoma (HCC) is a major public health problem in Egypt and remains an important cause of cancer-related mortality. The first-line treatment landscape for unresectable or advanced HCC has changed substantially with the introduction of immune checkpoint inhibitor-based regimens. Atezolizumab plus bevacizumab and durvalumab plus tremelimumab (STRIDE regimen) are both used as first-line systemic treatment options. However, there is no prospective head-to-head trial directly comparing these two regimens in Egyptian patients. Real-world local data are therefore needed to support treatment selection in routine clinical practice.

This is a retrospective, observational cohort study conducted at Suhag Cancer Center, Egypt. The study compares the real-world effectiveness, safety, and health-related quality of life outcomes of atezolizumab plus bevacizumab versus durvalumab plus tremelimumab in adults with locally advanced or metastatic HCC who received either regimen as first-line systemic therapy.

The study population includes eligible patients who initiated either atezolizumab plus bevacizumab or durvalumab plus tremelimumab between January 2021 and December 2024. Patients must be 18 years or older, have histologically or radiologically confirmed HCC according to international diagnostic guidelines, have an Eastern Cooperative Oncology Group performance status of 0 or 1, have locally advanced or metastatic disease not amenable to curative surgical or locoregional treatment, and have at least one follow-up visit with complete clinical and radiologic records available.

Patients will be excluded if they are younger than 18 years; have an Eastern Cooperative Oncology Group performance status of 2 or higher; have autoimmune disease requiring systemic immunosuppressive therapy; have prior liver transplantation or another active malignancy within the past three years, except localized skin cancer or cervical carcinoma in situ; have known HIV infection or uncontrolled active hepatitis B or C viremia; have uncontrolled cardiovascular or thromboembolic disease such as recent myocardial infarction, stroke, or pulmonary embolism within 6 months; have known central nervous system metastases or leptomeningeal disease; or are pregnant or lactating.

Data will be retrospectively retrieved from the Suhag Cancer Center cancer registry and hospital medical records. Extracted variables will include demographic characteristics, clinical characteristics, treatment details, response assessments, survival outcomes, adverse events, and health-related quality of life information. Clinical variables will include age, sex, Eastern Cooperative Oncology Group performance status, Child-Pugh score, Barcelona Clinic Liver Cancer stage, vascular invasion, and extrahepatic metastases. Treatment variables will include regimen type, number of cycles received, dose modifications, and reasons for treatment discontinuation.

The primary endpoint is the 12-month overall survival rate. Overall survival will be measured from the start date of first-line systemic therapy to death from any cause or last known follow-up. Secondary endpoints include median progression-free survival, objective response rate, disease control rate, duration of response, grade 3 or higher treatment-related adverse events, and health-related quality of life. Progression-free survival will be measured from treatment initiation to radiologic progression or death. Tumor response will be assessed using RECIST 1.1 or modified RECIST criteria based on available imaging. Adverse events will be graded according to CTCAE version 5.0. Health-related quality of life will be evaluated using the validated EORTC QLQ-C30 questionnaire at predefined treatment and follow-up time points, when available. An exploratory analysis will assess the association between baseline alpha-fetoprotein levels and treatment outcomes, including overall survival, progression-free survival, and objective response rate.

The primary statistical hypothesis is that atezolizumab plus bevacizumab may demonstrate superior or non-inferior overall survival compared with the STRIDE regimen in patients with unresectable or metastatic HCC. Time-to-event outcomes will be summarized using Kaplan-Meier methods and compared using log-rank testing where appropriate. Cox proportional hazards models may be used to estimate hazard ratios with confidence intervals. Binary outcomes such as objective response rate and disease control rate may be compared using appropriate categorical tests or logistic regression models. Safety outcomes will be summarized descriptively and compared between treatment groups when feasible.

The planned retrospective comparison has an approximate 1:1 allocation between the two treatment groups. The analysis is exploratory and precision-oriented because the available sample size is limited and may not provide adequate power to detect modest survival differences. The analysis was based on data available at the interim cut-off date of July 1, 2025, with follow-up ongoing to complete the planned 24-month observation period.

The study protocol was reviewed and approved by the institutional ethics committee. Because the study uses existing medical records, informed consent for data review was waived. All patient data will be anonymized and handled confidentially according to applicable ethical principles and data protection requirements.

Inclusion criteria

• Age 18 of informed consent.
• Laboratory and radiologically confirmed diagnosis of unresectable or metastatic hepatocellular carcinoma.
• No prior systemic therapy for HCC.
• Child-Pugh liver function class A (score 5-6).
• ECOG performance status of 0 or 1.
• Adequate haematologic and organ function as defined by: o Hemoglobin ≥ 9 g/dL o Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L o Platelets ≥ 75 × 10⁹/L o Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min o AST and ALT ≤ 5 × ULN (≤ 3 × ULN if no liver involvement) o ULN Total bilirubin ≤ 2 × 7.
• Willingness to comply with study procedures and follow-up schedule.
• Signed written informed consent obtained prior to any study-related procedures.

Exclusion criteria

• History of autoimmune disease requiring systemic immunosuppressive therapy.
• Untreated or high-risk gastro-oesophageal varices as defined by institutional standards.
• Prior liver transplantation or diagnosis of another active malignancy (excluding localized skin cancer or cervical carcinoma in situ) within the past three years.
• Patients with high-risk oesophageal varices.
• Patients with portal vein thrombosis.
• Known HIV infection or active hepatitis B/C with uncontrolled viraemia.
• Uncontrolled cardiovascular or thromboembolic disease (e.g., recent myocardial infarction, stroke, or pulmonary embolism within 6 months).
• Active bleeding, coagulopathy, or platelet disorders contraindicating bevacizumab.
• Lactation.
• Pregnancy.