Hepatobiliary Cancers
Conditions
Keywords
Hepatobiliary cancer, Unresectable hepatocellular carcinoma (uHCC), embolization eligible uHCC (eeHCC), Advanced biliary tract cancer (aBTC), Durvalumab, Observatory, Real-world
Brief summary
Given the number of anticipated durvalumab-based treatment launches in the hepatobiliary cancer space over the next 3 years, there is a need to capture contemporary real-world data across these indications. LIVER-R is a multi-country, multi-center, observational study of patients with a confirmed diagnosis of hepatobiliary cancer treated with or without a durvalumab-based regimen as part of routine clinical practice or early access program (EAP). The study design will include primary and secondary data collection. The primary objective of this study is to evaluate the effectiveness of regimens (durvalumab-based or otherwise) in real-world settings as measured by real-world overall survival. Other endpoints include demographics, clinical characteristics, clinically significant events of interest, treatment patterns, concomitant medications, treatment provider characteristics, and other real-world clinical endpoints (such as duration of treatment, progression-free survival, time to treatment progression, time to next treatment, time to treatment discontinuation, recurrence-free survival, and time to treatment recurrence).
Detailed description
LIVER-R is a real-world, multi-country, multi-centre study aiming to enroll approximately 4,000 patients across hepatobiliary cohorts (approximately 1,385 patients for aBTC, approximately 1,165 patients for uHCC, approximately 1,000 patients for eeHCC, and approximately 400 patients for EMERALD) across multiple countries from North and South America, Europe, the Middle East and the Asia-Pacific region. The study design will include primary and secondary data collection. Primary data will be collected in real-time during the patient's routine visit. Secondary data will be collected from the patient's medical record at enrollment and at prespecified study time points (6-month intervals). The study population includes adult patients whose physician has previously made the decision to treat them with or without a durvalumab-based regimen for hepatobiliary cancer as part of routine clinical practice or patients receiving treatment through EAP. The study will include a baseline period of up to 5 years before the index date (initiation of a durvalumab-based or non durvalumab-based regimen) and a follow-up period to the earliest of death, loss to follow-up, withdrawal, or end of study for a minimum follow-up of 2 years. This is a descriptive, noncomparative study. No formal hypotheses are to be tested. All descriptive analyses will be conducted separately for each primary hepatobiliary cancer indication. Kaplan Meier estimates will be produced for time-to-event outcomes.
Interventions
OTHERDurvalumab-based combination therapies in observational study setting
Data on patients who initiated durvalumab-based regimens, including STRIDE (Single Tremelimumab Regular Interval Durvalumab), will be collected).
OTHERNon Durvalumab-based therapies in observational study setting
Data on patients who initiated non durvalumab-based regimens, including LRT alone or LRT followed by systemic therapies, will be collected.
OTHERDurvalumab-based combination therapies in observational study settings
Data on patients who initiated durvalumab-based regimens in combination with LRT, will be collected
Sponsors
AstraZeneca
ICON plc
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria All patients must meet all of the following general criteria 1-4 along with all respective cohort specific criteria noted below: 1. Age ≥18 years and a lawful adult in the country at the index date 2. Confirmed presence of malignancy of primary hepatobiliary cancer by any method (e.g., radiological, histological, etc.) 3. Decision to treat was made independently and prior to obtaining informed consent 4. Informed consent was obtained as per country level regulations (includes waiver of consent for retrospective data collection if approved) aBTC Specific Inclusion Criteria A patient will be eligible to be included in the aBTC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria: 1. Patient has unresectable aBTC 2. Has received or is intending to receive a durvalumab-based regimen (may have been treated in an EAP) uHCC Specific Inclusion Criteria A patient will be eligible to be included in the uHCC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria: 1. Patient has unresectable uHCC 2. Not eligible for LRT, as well as for those who progressed following LRT 3. Has received or is intending to receive a durvalumab-based regimen (may have been treated in an EAP) eeHCC Specific Inclusion Criteria A patient will be eligible to be included in the eeHCC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria: 1. HCC confirmed by radiological or histological diagnosis 2. Child-Pugh A-B7 3. Disease not amenable to curative treatment but amenable to LRT at index 4. Patients with liver-confined HCC who initiated first non-curative intent LRT on or after 01 January 2024 5. Patients eligible for LRT with palliative intent such as TACE/ TARE/transarterial infusion chemotherapy (TAIC)/ hepatic arterial infusion chemotherapy (HAIC)/transarterial embolization (TAE) given by itself or in combination with other systemic therapy (can include durvalumab) within 60 days of the LRT EMERALD Specific Inclusion Criteria A patient will be eligible to be included in the EMERALD cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria: 1. HCC confirmed by radiological or histological diagnosis 2. Child-Pugh score of A-B7 3. Liver-confined disease not amenable to curative treatment but amenable to LRT at index 4. Receipt of a durvalumab-based regimen in combination with LRT administered within 28 days of each other (index is the first of the two treatments administered)
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Real-world overall survival (rwOS) in all participants | rwOS will be assessed as OS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median OS for a minimum follow-up of 2 years. | rwOS will be calculated as the time from the index date to date of death, by any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically significant events (CSEs) of interest leading to a medical intervention in all participants | CSEs will be captured from the index date through 90 days after the last administration of durvalumab-based or non durvalumab-based regimens or death, whichever occurs first. | CSEs of interest leading to medical intervention including treatment interruption, discontinuation, hospitalization, or which require interventions of concomitant use of corticosteroids, immunosuppressants and/or endocrine therapies will be captured for the enrolled patients. |
| Patient demographic and clinical characteristics in all participants | Patient demographic and clinical characteristics will be captured up to 5 years prior to the index date. | Descriptive statistics will be used to describe demographic and clinical characteristics for the enrolled patients. |
| Characterize the durvalumab-based regimen and/or LRT treatment patterns in all participants | Treatment patterns will be captured from the index date until the earliest of death, loss to follow-up, withdrawal, or end of study for a minimum follow-up of 2 years. | Treatment patterns of the index durvalumab-based regimen or LRT will be described. Treatment patterns of therapies administered both before and after the first administration of index durvalumab-based regimen or LRT will be described. |
| Real-world duration of treatment (rwDOT) in all participants | rwDOT will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median DOT for a minimum follow-up of 2 years. | rwDOT will be calculated as the time from the index date to date of discontinuation of the index durvalumab-based regimen or LRT. |
| Real-world progression free survival (rwPFS) in all participants | rwPFS will be assessed as PFS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median PFS for a minimum follow-up of 2 years. | rwPFS will be calculated as the time from the index date to the earliest date of documented disease progression as determined by the physician's assessment or death. |
| Real-world time to progression (rwTTP) in all participants | rwTTP will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTP for a minimum follow up of 2 years. | rwTTP will be calculated as the time from the index date to the date of documented disease progression as determined by the physician's assessment. |
| Real-world time to next treatment (rwTTNT) in all participants | rwTTNT will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTNT for a minimum follow-up of 2 years. | rwTTNT will be calculated as the time from the index date (first-line treatment date) to the date of initiation of the next treatment. rwTTNT will also be assessed for subsequent lines of therapy among patients who started a second line of therapy until a third line of therapy, patients who started a third line of therapy until a fourth line of therapy (rwTTNT), etc. |
| Real-world time to treatment discontinuation (rwTTD) in all participants | rwTTD will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTD for a minimum follow-up of 2 years. | rwTTD will be calculated as the time from index date until discontinuation of treatment for any reason, including disease progression, toxicity, and death. |
| Characterization of providers among all participants | Provider characteristics will be captured up to 5 years prior to the index date | Descriptive statistics will be used to describe provider characteristics: academic vs. community. |
| Real-world recurrence free survival (rwRFS) in aBTC and uHCC | rwRFS will be assessed as RFS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median RFS for a minimum follow-up of 2 years. | rwRFS will be defined as the time from the index date to the earliest date of documented disease recurrence as determined by the physician's assessment or death, whichever is earlier. The analysis will be performed in patients who underwent curative therapy (resection or ablation). |
| Real-world time to recurrence (rwTTR) in aBTC and uHCC | rwTTR will be assessed as recurrence rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTR for a minimum follow-up of 2 years. | rwTTR will be defined as the time from the index date to the date of documented disease recurrence as determined by the physician's assessment. The analysis will be performed in patients who underwent curative therapy (resection or ablation). |
| Liver function over time in eeHCC and EMERALD | Liver function will be assessed as the change in liver function markers for a minimum follow-up of 2 years | Liver function markers over time will be examined including the closest measure to the index date in the baseline period of first LRT, from pre-treatment through the follow-up period. The primary summary of interest is the change (or trajectory) in liver function markers (ALBI score and Child-Pugh score) over time. |
| Clinical characteristics in EMERALD and eeHCC | Clinical characteristics will be assessed descriptively for a minimum follow-up of 2 years. | The percentage of participants who receive subsequent curative resection or liver transplant will be described. |
| Provider specialty and treatment patterns in eeHCC | Provider specialty will be assessed descriptively and treatment patterns will be assessed as a percentage of participants for a minimum follow-up of 2 years | Provider specialty characteristics will be described. The percentage of participants receiving LRT as subsequent line of treatment (among participants receiving only LRT as standard of care). |
Countries
Australia, Austria, Belgium, Brazil, Canada, France, Germany, Greece, Israel, Italy, Japan, Norway, Portugal, Puerto Rico, Romania, Saudi Arabia, Singapore, Spain, Switzerland, Taiwan, United Arab Emirates, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed