Durvalumab (6) – Imfinzi®
Hepatocellular carcinoma, first-line, monotherapy
Characteristics
| Start date | 15.12.2023 – Marketing authorisation: 15.11.2023 |
|---|---|
| Resolution | 06.06.2024 |
| Limitation date | 01.01.2025 limitation repealed |
| INN | Durvalumab |
| Brand name | Imfinzi® |
| Pharm. company | AstraZeneca GmbH |
| G-BA Procedure ID | D-1009 |
| ATC code | L01FF03 PD-1/PDL-1 inhibitors (L01FF) |
| ICD-10 codes (AIS) | C22.0Hepatocellular carcinoma |
| Alpha-ID codes (AIS) | I24287Hepatocellular carcinoma |
| Therapeutic area | Oncological diseases Hepatocellular carcinoma (HCC) |
| Reason for procedure | New therapeutic indication |
| Specialty | ACT change |
| Therapeutic indication of the resolution |
|---|
|
Imfinzi as monotherapy is indicated in adults for the first-line treatment of advanced or unresectable hepatocellular carcinoma (HCC) |
| Subpopulation | Indication | Comparator |
|---|---|---|
| a) | Adults with advanced or unresectable hepatocellular carcinoma (HCC) with Child-Pugh A or no liver cirrhosis; first-line therapy | - Atezolizumab in combination with bevacizumab or – Durvalumab in combination with tremelimumab |
| b) | Adults with advanced or unresectable hepatocellular carcinoma (HCC) with Child-Pugh B; first-line therapy | Best supportive care |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (HIMALAYA) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. non-ACT + ITC (Bucher) |
|
Meta analysis
(best subpopulation) |
no |
| ACT change | 17.04.2024 – Stellungnahme der Fachgesellschaften |
- Clinical trials
- The HIMALAYA trial is an open-label, randomised, controlled trial comparing durvalumab as monotherapy or durvalumab in combination with tremelimumab against sorafenib, with four treatment arms.
- The IMbrave150 trial is an open-label, randomised, controlled Phase III trial conducted from 2018 to 2022 at 111 trial centres in Asia, Australia, Europe and North America.
a) Adults with advanced or unresectable hepatocellular carcinoma (HCC) with Child-Pugh A or no liver cirrhosis; first-line treatment
- An additional benefit is not proven.
- Overall, additional benefit for durvalumab (monotherapy) compared with atezolizumab in combination with bevacizumab is not proven in adults with advanced or unresectable HCC with Child-Pugh A or no liver cirrhosis.
- mortality
- For the endpoint of overall survival, the adjusted indirect comparison shows no statistically significant difference between durvalumab (monotherapy) and atezolizumab plus bevacizumab.
- There is therefore no proof of additional benefit for durvalumab compared with atezolizumab plus bevacizumab in terms of overall survival.
- Morbidity and health-related quality of life
- No suitable data are available for an indirect comparison of the endpoints in the categories of morbidity and quality of life.
- Differences in follow-up durations are evident in both the HIMALAYA study and the IMbrave150 study. Therefore, in the present situation, analyses of time to first deterioration should be used. However, such analyses are only available for the IMbrave150 study.
- Furthermore, for all the aforementioned endpoints relating to morbidity and health-related quality of life, there is a high potential for bias – at least due to the lack of blinding in the assessment of subjective endpoints – meaning that the requirement for certainty of results necessary to carry out an adjusted indirect comparison would not be met.
- Side effects
- Overall, there is no advantage or disadvantage of durvalumab compared with atezolizumab + bevacizumab in terms of side effects.
- For the SAE endpoint, the adjusted indirect comparison shows no statistically significant difference between durvalumab (monotherapy) and atezolizumab + bevacizumab.
- For severe AEs, there is a systematic difference in the duration of observation between the two studies. This gives rise to uncertainties in the interpretation of the results from the indirect comparison for the endpoint of severe AEs.
- For the endpoint ‘discontinuation due to AEs’, the open-label study design leads to a high potential for bias.
- Due to the low certainty of the results, the requirements for an indirect comparison are not met.
- No data, or no suitable data, are available for the endpoints PRO-CTCAE, bleeding and immune-mediated AEs.
- Overall assessment
- For the assessment of the additional benefit of durvalumab (monotherapy) compared with atezolizumab in combination with bevacizumab in adults with advanced or unresectable HCC with a Child-Pugh A or no liver cirrhosis, results are available from the adjusted indirect comparison of the HIMALAYA study with the IMbrave150 study using sorafenib as the bridging comparator.
- No statistically significant difference was observed for the endpoint of overall survival.
- The data on morbidity and quality of life collected in the individual studies are not suitable for the adjusted indirect comparison.
- Overall, there is no advantage or disadvantage of durvalumab compared with atezolizumab + bevacizumab in terms of side effects. There are uncertainties regarding the interpretation of the results for the endpoint of severe AEs. No suitable data are available for the endpoint of discontinuation due to AEs.
- Overall review
- In the overall review, additional benefit is not proven for durvalumab (monotherapy) compared with atezolizumab in combination with bevacizumab in adults with advanced or unresectable HCC with Child-Pugh A or no liver cirrhosis.
b) Adults with advanced or unresectable hepatocellular carcinoma (HCC) with Child-Pugh B; first-line treatment
- An additional benefit is not proven.
- For adults with advanced or unresectable hepatocellular carcinoma (HCC) with Child-Pugh B in first-line treatment, the pharmaceutical manufacturer has not submitted any data for the assessment of additional benefit. Consequently, additional benefit is not proven.
Courtesy translation only, please refer to the German original.
Associated procedures
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