The Era of Hormone Suppression Alone in Metastatic Prostate Cancer Treatment Is Ending

New data presented at the ESMO 2021 Congress on treating previously untreated men with metastatic, castration-sensitive (hormone suppression-sensitive) prostate cancer are set to change our clinical practice.

Newly diagnosed patients who have not received hormonal treatment (androgen suppression) and have metastatic prostate cancer are described as having castration-sensitive prostate cancer. This group includes patients with metastases in bones and other organs and patients who previously had surgery or regional radiotherapy for prostate cancer without any hormonal treatment and subsequently developed recurrent metastatic disease.

In recent years, two important advances have occurred in treating recurrent or newly diagnosed metastatic prostate cancer that has not received hormonal treatment:

• the first is adding the chemotherapy drug docetaxel to conventional hormonal treatment;
• the other is adding the next-generation hormonal treatment abiraterone acetate to conventional hormonal treatment.

These two treatment strategies have been shown, in high-risk patients, to be superior to conventional hormonal treatment used for years. These advances also raised an important question:

What happens if we add both abiraterone and docetaxel to conventional hormonal treatment? The PEACE-1 study was conducted to answer this question.

A Standout Study at ESMO

These new results from the PEACE-1 clinical trial show that adding abiraterone (Zytiga) plus docetaxel chemotherapy to standard hormone suppression has a clinically meaningful effect on survival, with significant improvements in both radiological progression-free survival and overall survival. Long-term results from this study were presented at ESMO 2021.

With this triplet combination (hormone suppression + abiraterone + docetaxel), radiological progression-free survival showed a median improvement of 2.5 years and a 25% reduction in the risk of death was reported. These results were significant despite a large proportion of patients in the standard-treatment arm switching to the abiraterone arm during the study.

Design of the PEACE-1 Study

Since 2015, standard treatment for men with metastatic castration-sensitive prostate cancer has been adding docetaxel, abiraterone or androgen-signaling inhibitors such as enzalutamide (Xtandi) to hormonal treatment, or radiotherapy to the primary tumor in men with a low metastatic burden.

Until these new PEACE-1 results, it was unclear whether hormone suppression plus a “combination of other treatments” could improve outcomes further.

In the study, standard treatment was defined as hormonal treatment with or without docetaxel.

The study arms were:

• standard treatment alone (296 patients),
• abiraterone plus standard treatment (292 patients),
• radiotherapy plus standard treatment (293 patients), and
• radiotherapy plus abiraterone plus standard treatment (292 patients).

The Risk of Cancer Progression Was Halved

In patients receiving hormone suppression plus docetaxel plus abiraterone, with or without radiotherapy, median radiological progression-free survival was 4.5 years, compared with 2 years in those receiving standard care alone. This corresponds to abiraterone reducing the risk of cancer progression by 50% (HR: 0.50; P < 0.0001).

For men with a high metastatic burden, median radiological progression-free survival was 4.1 years with abiraterone, compared with 1.6 years with standard care alone (HR, 0.47; P < 0.0001).

However, the benefit was less clear for men with low-volume metastases because there were relatively few progression or death events among these patients. Median radiological progression-free survival had not been reached among men in this group receiving abiraterone plus standard care; it was 2.7 years in those treated with standard care alone.

Side effects occurring more frequently with abiraterone were liver toxicities, hypertension and hypokalemia (low potassium).

Comment

The strengths of PEACE-1 are its integrative strategy, which helps address previously unanswered questions, and its use of treatments already available.

However, it remains unclear how hormone suppression plus docetaxel plus abiraterone compares with hormone suppression plus abiraterone alone.

In summary, these latest data from PEACE-1 and other studies with docetaxel and androgen-signaling inhibitors indicate that treating men with metastatic castration-sensitive prostate cancer with hormone suppression alone is no longer acceptable.

For this group of patients, the current ideal treatment options are:

• Hormone suppression plus abiraterone, enzalutamide or apalutamide
• Hormone suppression plus docetaxel, and
• The triplet combination of hormone suppression plus docetaxel plus abiraterone, particularly for patients with high-volume disease.

More data are needed on the potential combination of hormone suppression plus docetaxel and apalutamide or enzalutamide.