Evaluating the effectiveness of enzalutamide plus androgen deprivation therapy in metastatic hormone-sensitive prostate cancer by pattern of metastatic spread

This study examined the impact of the pattern of metastatic spread on the effectiveness of enzalutamide in combination with androgen deprivation therapy (ADT) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). The data showed that the combination has good outcomes in men with bone and/or lymph node metastases.

Patients with mHSPC have prostate cancer that has spread beyond the prostate gland. Generally, these patients are treated with hormone therapy such as ADT. ADT reduces the production of androgens (male sex hormones such as testosterone). Reducing these androgens prevents cancer cell growth.

Enzalutamide is an anti-androgen medication. It blocks testosterone from reaching PC cells. It is used for the treatment of mHSPC. Enzalutamide plus ADT has been shown to improve clinical outcomes in men with mHSPC. However, whether the pattern of metastatic spread impacts the effectiveness of enzalutamide plus ADT is not known yet.

This study involved 1146 men with mHSPC. Patients were randomly assigned to receive either enzalutamide plus ADT or placebo plus ADT. 513 men had metastases only to the bones. 351 patients had metastases to the bones and lymph nodes. 154 men had metastases to the lymph nodes only. The other 128 patients had metastases to other organs, with or without bones and lymph node metastases. Patients were followed up for an average of 11.5-13.7 months.

Enzalutamide plus ADT significantly lowered the risk of progression or death by 67% versus placebo plus ADT in men with bone-only metastases and by 69% in men with bone plus lymph node metastases. 

Also, significantly, more patients in enzalutamide plus ADT (52.6%-80.0%) achieved undetectable prostate-specific antigen (PSA) levels (a marker of prostate cancer) compared to those who received placebo plus ADT (10.3%-26.1%).

This study concluded that treatment with enzalutamide plus ADT provided improvements in men with mHSPC and bone and/or lymph node metastases. 

This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide. The short duration of follow-up and small sample sizes can limit conclusions.