Talazoparib with enzalutamide for untreated hormone-relapsed metastatic prostate cancer [ID4004]

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 *12.Prostate cancer is the most common cancer in men *3 and the incidence increases with age.

It is more common in those who have a family history of prostate cancer in black African men compared to white men and is least common in Asian men *1.In England and Wales around 45885 people were newly diagnosed with prostate cancer between 2019 and 2020 *4. Of this 13% had metastatic disease that is disease that has spread to other parts of the body (such as the bones) *4.

In 2019around 12000 people died from prostate cancer *5.NICE clinical guideline 131 recommends radical treatment (surgery and radiotherapy) and androgen deprivation therapy (ADT) for the treatment of local and locally advanced prostate cancer. The aim of ADT is to suppress androgen levels and cause prostate cancer cell death.

This can be achieved by orchidectomy (surgical removal of the testes) or by hormonal treatments such as luteinising hormone-releasing hormone agonist (e.g. goserelin) and antagonist (e.g. degarelix) and androgen receptor inhibitor (e.g. bicalutamide).

For newly diagnosed metastatic prostate cancer cases docetaxel (chemotherapy) can be offered within 12 weeks of starting ADT.

In other metastatic cases ADT is recommended initially.Prostate cancer may initially be responsive to hormone therapy but eventually become resistant to it.

This is known as hormone-relapsed prostate cancer (also known as hormone-resistant hormone-refractory and castration-resistant) and refersto prostate cancer which has progressed following ADT.

Hormone-relapsed prostate cancer is characterised by a rise in prostate-specific antigen (PSA) despite ADT.New hormonal agents (NHAs) refer to recently developed medicines which decrease androgen levels. These include apalutamide enzalutamide darolutamide and abiraterone. Two treatments are currently recommended for hormone-relapsed metastatic prostate cancer before chemotherapy.

Enzalutamide is recommended for treating hormone-relapsed metastatic prostate cancer after ADT has failed and before chemotherapy is indicated (TA377).

Similarly abiraterone in combination with prednisone or prednisolone is recommended for treating hormone-relapsed metastatic prostate cancer in people who have no or mild symptoms after ADT has failed and before chemotherapy is indicated (TA387).Olaparib is recommended for treating hormone-relapsed metastatic prostate cancer with BRCA1 or BRCA2 mutations that has progressed after a newer hormonal treatment such as abiraterone or enzalutamide (TA887).

Olaparib with abiraterone and prednisone or prednisolone is recommended as an option for untreated hormone-relapsed metastatic prostate cancer in adults who cannot have or do not want chemotherapy (TA951).

Chemotherapy docetaxel is recommended for people with hormone-relapsed metastatic prostate cancer with a Karnofsky Performance Status Score of 60% or more (NICE clinical guideline 131 and TA101).Abiraterone in combination with prednisone or prednisolone is recommended for the treatment of hormone-relapsed metastatic prostate cancer if the disease has progressed on or after one course of docetaxel-containing regimen (TA259).

Enzalutamide is also recommended for treating hormone-relapsed metastatic prostate cancer in adults whose disease has progressed during or after docetaxel containing chemotherapy (TA316).Cabazitaxel in combination with prednisone or prednisolone is recommended for treating hormone-relapsed metastatic prostate cancer in people whose disease has progressed during or after docetaxel chemotherapy (TA391).

Radium-223 dichloride is recommended as an option for treating hormone-relapsed prostate cancer in people with symptomatic bone metastases and no known visceral metastases if they have already had docetaxel or if docetaxel is contraindicated or unsuitable (TA412).References*1. Cancer Research UK (2022) Prostate cancer risks and causes.

Accessed May 2024.2. Macmillan Cancer Support (2021) Potential causes of prostate cancer. Accessed May 2024.3. Cancer Research UK (2018) Prostate cancer incidence statistics. Accessed May 2024.4. National Prostate Cancer Audit (2022) Annual Report 2021. Accessed May 2024.5. Cancer Research UK (2019) Prostate cancer mortality statistics.

Accessed May 2024.