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

This retrospective observational study compares two first-line immunotherapy-based treatment regimens used for adults with locally advanced or metastatic hepatocellular carcinoma (HCC) at Suhag Cancer Center, Egypt. The two regimens are atezolizumab plus bevacizumab and durvalumab plus tremelimumab, also known as the STRIDE regimen. HCC is a major cancer burden in Egypt. Although both regimens have shown benefit in international clinical trials, they have not been directly compared in Egyptian patients. Differences in local disease patterns, comorbidities, access to treatment, and real-world tolerability may influence treatment outcomes. This study will use existing medical records and cancer registry data to compare outcomes between patients who received either regimen as first-line systemic therapy. The primary aim is to compare the 12-month overall survival rate between the two treatment groups. Secondary aims include comparing progression-free survival, tumor response, disease control, severe treatment-related adverse events, and health-related quality of life. Tumor response will be assessed using RECIST 1.1 or modified RECIST criteria when available, and adverse events will be graded according to CTCAE version 5.0. Eligible patients are adults with confirmed locally advanced or metastatic HCC who were not candidates for curative surgical or locoregional treatment and who started one of the two regimens between January 2021 and December 2024. Data will be collected retrospectively from registry and hospital records. Because this is a retrospective review of existing records, informed consent was waived by the institutional ethics committee, and patient data will be handled confidentially and anonymized.

Sex

All

Minimum age

18 Years

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.

• RESULTSangro B, Chan SL, Kelley RK, Lau G, Kudo M, Sukeepaisarnjaroen W, Yarchoan M, De Toni EN, Furuse J, Kang YK, Galle PR, Rimassa L, Heurgue A, Tam VC, Van Dao T, Thungappa SC, Breder V, Ostapenko Y, Reig M, Makowsky M, Paskow MJ, Gupta C, Kurland JF, Negro A, Abou-Alfa GK; HIMALAYA investigators. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Ann Oncol. 2024 May;35(5):448-457. doi: 10.1016/j.annonc.2024.02.005. Epub 2024 Feb 19. PMID 38382875
• RESULTAbou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, Sukeepaisarnjaroen W, Kang YK, Van Dao T, De Toni EN, Rimassa L, Breder V, Vasilyev A, Heurgue A, Tam VC, Mody K, Thungappa SC, Ostapenko Y, Yau T, Azevedo S, Varela M, Cheng AL, Qin S, Galle PR, Ali S, Marcovitz M, Makowsky M, He P, Kurland JF, Negro A, Sangro B. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022 Aug;1(8):EVIDoa2100070. doi: 10.1056/EVIDoa2100070. Epub 2022 Jun 6. PMID 38319892
• RESULTFinn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745. PMID 32402160