TA903/Scope
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Appendix B

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE

Health Technology Evaluation

Darolutamide with androgen deprivation therapy and docetaxel for treating hormone-sensitive metastatic prostate cancer

Final scope

Remit/evaluation objective

To appraise the clinical and cost effectiveness of darolutamide with androgen deprivation therapy and docetaxel within its marketing authorisation for treating hormone-sensitive metastatic prostate cancer.

Background

Prostate cancer is a condition in which tumours develop in the prostate, a gland in the male reproductive system. The exact cause is unknown but environmental and genetic factors are associated with an increased risk of developing prostate cancer.[1,2]

The incidence of prostate cancer increases with age and is higher in people of black African-Caribbean family origin and people with a family history of the condition.[1] In England, between 2019 and 2020, 43,330 people were diagnosed with prostate cancer. Of those, 13% of people diagnosed had metastatic disease, that is, disease that has spread to other parts of the body (for example, the bones).[3 ] The age standardised mortality rate for prostate cancer in 2019 was 45.5 for every 100,000 persons.[4]

NICE clinical guideline 131 (NG131) classifies localised prostate cancer to be at low, intermediate or high risk of progression based on prostate-specific antigen concentration, Gleason score (based on a biopsy) and clinical stage. People with intermediate or high risk non-metastatic prostate cancer may be offered hormone therapy (also called androgen deprivation therapy). Prostate cancer may initially respond to hormone therapy but eventually become resistant to it. This clinical condition is described as ‘hormone-relapsed’ prostate cancer.

For newly diagnosed metastatic prostate cancer, NG131 recommends starting docetaxel chemotherapy within 12 weeks of starting androgen deprivation therapy. For metastatic prostate cancer, the guideline recommends offering bilateral orchidectomy as an alternative to continuous luteinising hormone-releasing hormone agonist therapy. For people who are willing to accept the adverse impact on overall survival and gynaecomastia (breast swelling) in the hope of retaining sexual function, the guideline recommends offering anti-androgen monotherapy with bicalutamide. NICE technology appraisal 404 recommends degarelix, a gonadotrophin-releasing hormone antagonist, for treating advanced hormone-dependent (hormone-sensitive) prostate cancer in people with spinal metastases. In addition, NICE technology appraisal 712 recommends enzalutamide plus androgen deprivation therapy as an option for treating hormone-sensitive metastatic prostate cancer in adults, and NICE technology appraisal 741 recommends apalutamide plus androgen deprivation therapy as an option for treating hormone-sensitive metastatic prostate cancer in adults, if docetaxel is not suitable.

Final scope for the evaluation of darolutamide with androgen deprivation therapy and docetaxel for treating hormone-sensitive metastatic prostate cancer Issue Date: July 2022 © National Institute for Health and Care Excellence 2022. All rights reserved.

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Appendix B

The description ‘hormone-sensitive metastatic prostate cancer’ refers to a population that includes people with metastatic prostate cancer who have not had androgen deprivation therapy, or whose disease is continuing to respond to androgen deprivation therapy.

The technology

Darolutamide (Nubeqa, Bayer) does not currently have a marketing authorisation in the UK for treating hormone-sensitive metastatic prostate cancer. Darolutamide with androgen deprivation therapy and docetaxel is being studied in a clinical trial, compared with placebo plus androgen deprivation therapy and docetaxel, in adults with hormone-sensitive metastatic prostate cancer.

Darolutamide does have a marketing authorisation in the UK for treating hormonerelapsed prostate cancer in adults at high risk of developing metastatic disease.

Intervention(s) Darolutamide with androgen deprivation therapy and
docetaxel
Population(s) People with hormone-sensitive metastatic prostate cancer
Subgroups If the evidence allows, the following subgroups of people will
be considered:

people with newly diagnosed metastatic prostate
cancer

people with high-risk metastatic prostate cancer.
Comparators
Androgen deprivation therapy alone (including
orchidectomy, luteinising hormone-releasing hormone
agonist therapy, degarelix, monotherapy with
bicalutamide)

Docetaxel with androgen deprivation therapy

Enzalutamide with androgen deprivation therapy
Outcomes The outcome measures to be considered include:

overall survival

progression-free survival

response rate

prostate-specific antigen response

time to prostate-specific antigen progression

adverse effects of treatment

health-related quality of life.

Final scope for the evaluation of darolutamide with androgen deprivation therapy and docetaxel for treating hormone-sensitive metastatic prostate cancer Issue Date: July 2022 © National Institute for Health and Care Excellence 2022. All rights reserved.

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Appendix B

Economic analysis The reference case stipulates that the cost effectiveness of
treatments should be expressed in terms of incremental cost
per quality-adjusted life year.
If the technology is likely to provide similar or greater health
benefits at similar or lower cost than technologies
recommended in published NICE technology appraisal
guidance for the same indication, a cost comparison may be
carried out.
The reference case stipulates that the time horizon for
estimating clinical and cost effectiveness should be
sufficiently long to reflect any differences in costs or
outcomes between the technologies being compared.
Costs will be considered from an NHS and Personal Social
Services perspective.
The availability of any commercial arrangements for the
intervention, comparator and subsequent treatment
technologies will be taken into account.
The availability and cost of biosimilar and generic products
should be taken into account.
Other
considerations
Guidance will only be issued in accordance with the
marketing authorisation. Where the wording of the therapeutic
indication does not include specific treatment combinations,
guidance will be issued only in the context of the evidence
that has underpinned the marketing authorisation granted by
the regulator.
Related NICE
recommendations
Related Technology Appraisals:
‘Apalutamide with androgen deprivation therapy for treating
hormone-sensitive metastatic prostate cancer’ (2021). NICE
Technology appraisal guidance [TA741]. Review date 2024.
‘Abiraterone for treating newly diagnosed high-risk hormone-
sensitive metastatic prostate cancer’ (2021). NICE
Technology appraisal guidance [TA721]. Review date 2024.
‘Enzalutamide for treating hormone-sensitive metastatic
prostate cancer’ (2021). NICE Technology appraisal guidance
[TA712]. Review date 2024.
‘Darolutamide with androgen deprivation therapy for treating
hormone-relapsed non-metastatic prostate cancer’(2020).
NICE Technology appraisal guidance [TA660]. Review date
2023.
Related Guidelines:
‘Prostate cancer: diagnosis and management’ (2019). NICE
guideline [NG131].
Related Quality Standards:
‘Prostate cancer’ (2015). NICE quality standard [QS91].

Final scope for the evaluation of darolutamide with androgen deprivation therapy and docetaxel for treating hormone-sensitive metastatic prostate cancer Issue Date: July 2022

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Appendix B

Related National
Policy
The NHS Long Term Plan, 2019.NHS Long Term Plan
NHS England (2018/2019)NHS manual for prescribed
specialist services (2018/2019)
NHS England (2021)Clinical Commissioning Policy: External
beam radiotherapy for patients presenting with hormone
sensitive, low volume metastatic prostate cancer at the time
of diagnosis
NHS England (2016)Clinical Commissioning Policy
Statement: Docetaxel in combination with androgen
deprivation therapy for the treatment of hormone naïve
metastatic prostate cancer
NHS England (2013)2013/14 NHS standard contract for
cancer: chemotherapy (adult)

References

  1. Cancer Research UK (2022) Prostate cancer risks and causes. Accessed April 2022.

  2. Macmillan Cancer Support (2022) Potential causes of prostate cancer. Accessed April 2022.

  3. National Prostate Cancer Audit (2021) Annual report 2021. Accessed April 2022.

  4. NHS Digital (2022). Cancer registration statistics, England 2019. Accessed April 2022

Final scope for the evaluation of darolutamide with androgen deprivation therapy and docetaxel for treating hormone-sensitive metastatic prostate cancer Issue Date: July 2022