The Epidemiology of Patients Treated With ATZ+BEV in Real Life Setting

Official title

A Multi-Centric, Retrospective, Real-World Study on First-Line Therapy With Atezolizumab Plus Bevacizumab for Advanced or Unresectable Hepatocellular Carcinoma in Romanian Population

Overview

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death globally. This retrospective, multicentric study will be coordinated by Dr. Adrian Radu Vidra (Lead Investigator) from Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor" Cluj-Napoca (Coordinating Site) to further investigate the clinical and demographic profile of patients receiving first-line treatment with atezolizumab and bevacizumab in the real-world setting of clinical practice from Romania. Participants already taking the combination therapy as part of their regular medical care for HCC will be followed during 3 years.

Detailed description

The available information suggests that the ATZ plus BEV is safe and effective as first-line systemic therapy for patients with unresected HCC and advanced HCC. The overall efficacy and safety of the combination has been well established in the literature and from the various clinical studies. This combination has since replaced tyrosine kinase inhibitors as the standard for many patients. The combination significantly increases OS (median 19.2 months vs. 13.4 months with sorafenib) and objective response rates (30% vs. 11%), offering better disease control.

The defined primary study outcome is describing the epidemiology of patients treated with ATZ+BEV in real-life setting.

History of the disease, including etiology of liver disease, BCLC stage, MVI, EHS, Child-Pugh Score, ALBI grade, MELD, Betablocker medication, Prior treatment, Resection, Local ablation, TACE/SIRT, BMI, ALT, AST, TBL, Albumin, INR, AFP will be collected and presented.

Data on baseline characteristics, radiological response, treatment patterns and adverse events will be summarized using descriptive statistics. Continuous variables will be presented shown as median and full range, and categorical variables will be reported as frequencies and percentages.

Median duration of therapy was defined as the time from the first administration until the last administration of the drugs. Patients who still received atezolizumab with or without concomitant bevacizumab at data cut-off will be censored.

Patients with at least one staging imaging assessment will be evaluated for radiological response.

Data from patients, who died without radiologically confirmed tumor progression, will be censored at the date of the last radiological assessment or death.

PFS is defined as the time from the date of the first therapy administration until radiological disease progression or death, whatever occurred first. Patients still alive and without radiologically confirmed progression at the date of the last contact or data cut-off will be censored.

OS will be defined as the time from the start of the treatment with atezolizumab and bevacizumab until the date of death.

Survival curves will be calculated with the Kaplan-Meier method and compared by means of the log-rank test.

Safety assessment will consist of monitoring the incidence of all adverse events observed following the treatment with ATZ plus BEV, graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5. Safety events will be stratified by type of events, grades, seriousness and will be collected at time points defined in the study flowchart.

Primary outcome measures

• Description of the epidemiology of patients treated with ATZ+BEV [Time frame: 36 months]

Secondary outcome measures (6)

• Progression-Free Survival (PFS) according to viral and non-viral etiology in the selected cohort [Time frame: 36 months]
• Overall Survival (OS) for patients treated with the combination therapy [Time frame: 36 months]
• Disease Control Rate (DCR) [Time frame: 36 months]
• Objective Response Rate (ORR) [Time frame: 36 months]
• Duration of Response (DOR) [Time frame: 36 months]
• Overall safety of the combined therapy [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

• Adult women and men (≥ 18 years of age) with proven initial diagnosis of HCC with evidence of loco-regional recurrent or advanced disease not amenable to resection.
• At least one cycle of therapy with ATZ plus BEV.
• Eligible individuals will be required to have Baseline (pre-index) EGD available
• No prior systemic therapy for HCC.
• Evaluable disease as defined per modified Response Evaluation Criteria in Solid Tumours (mRECIST) V1.1 criterion (At least 1 evaluable CT result over the entire available index and post-index period, excluding the baseline).
• Patients identified from the patient registry in the hospital with treatment charts between April 1, 2022- December 31, 2024 (index date).
• Eligible individuals will be required to have data available prior to the index date (pre-index period; baseline characteristics).

Exclusion criteria

• A diagnosis of any other primary cancer prior to the index date
• ATZ plus BEV treatment as part of a clinical trial
• ATZ or BEV given off-label
• Patients with incomplete medical records
• Patients receiving other investigational drugs
• History of hepatic encephalopathy
• Patients with brain metastasis
• HBV and HBC co-infection

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Romania · 4 centers

• Fundeni Clinical Institute — Bucharest
• Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor" — Cluj-Napoca
• Regional Institute of Oncology — Iași
• Oncohelp — Timișoara

Publications

• Kulkarni AV, Tevethia H, Kumar K, Premkumar M, Muttaiah MD, Hiraoka A, Hatanaka T, Tada T, Kumada T, Kakizaki S, Vogel A, Finn RS, Rao PN, Pillai A, Reddy DN, Singal AG. Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis. EClinicalMedicine. 2023 Aug 30;63:102179. doi: 10.1016/j.eclinm.2023.102179. eColl PMID 37680945
• Storandt MH, Zemla TJ, Patell K, Naleid N, Gile JJ, Tran NH, Chakrabarti S, Jin Z, Borad M, Mahipal A. Atezolizumab plus bevacizumab as first-line systemic therapy for hepatocellular carcinoma: a multi-institutional cohort study. Oncologist. 2024 Nov 4;29(11):986-996. doi: 10.1093/oncolo/oyae142. PMID 38979643
• Bialecki ES, Di Bisceglie AM. Diagnosis of hepatocellular carcinoma. HPB (Oxford). 2005;7(1):26-34. doi: 10.1080/13651820410024049. PMID 18333158
• Pinero F, da Fonseca LG. Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups? World J Gastroenterol. 2021 Jun 28;27(24):3429-3439. doi: 10.3748/wjg.v27.i24.3429. PMID 34239261
• Singal AG, Ozgurdal K, Fan X, Vassilev Z, Pan X, Multani JK, Chen CC, Zhou Z, He J, Pisa F. Real-World Systemic Treatment Patterns after Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma in the United States. Cancers (Basel). 2023 Nov 22;15(23):5532. doi: 10.3390/cancers15235532. PMID 38067235
• Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. doi: 10.1016/j.jhep.2021.11.030. Epub 2021 Dec 11. PMID 34902530
• Qin S, Chen M, Cheng AL, Kaseb AO, Kudo M, Lee HC, Yopp AC, Zhou J, Wang L, Wen X, Heo J, Tak WY, Nakamura S, Numata K, Uguen T, Hsiehchen D, Cha E, Hack SP, Lian Q, Ma N, Spahn JH, Wang Y, Wu C, Chow PKH; IMbrave050 investigators. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, PMID 37871608
• Vogel A, Meyer T, Saborowski A. IMbrave050: the first step towards adjuvant therapy in hepatocellular carcinoma. Lancet. 2023 Nov 18;402(10415):1806-1807. doi: 10.1016/S0140-6736(23)01962-1. Epub 2023 Oct 23. No abstract available. PMID 37883983

Identifiers

NCT: NCT06903663 · MANIFEST-HCC-RO

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗