Worldwide, an estimated number of 1,414,259 men were diagnosed with prostate cancer in the year 2020 alone. Prostate cancer is the fourth most diagnosed cancer in the world. Men under 40 years are rarely diagnosed with prostate cancer, however, men above 65 years are at risk. About 50% of men diagnosed with local prostate cancer are likely to develop metastatic cancer during their lifetime.1 

Androgen deprivation therapy (ADT) is the first-line treatment of symptomatic metastatic prostate cancer which is universally accepted. The US FDA has approved ADT only as palliation of symptomatic metastases and as neoadjuvant therapy for radiation therapy, however, it is widely used in the community setting to treat prostate cancer in men.2 The LATITUDE trial reported a sustained improvement in overall survival of the high-risk metastatic patients with a median survival of 52 months following treatment with abiraterone acetate (1000 mg) plus prednisone (5 mg) once daily orally and ADT. The primary analysis of the STAMPEDE study presented in 2017 reported significant improvements in overall survival and progression-free survival with abiraterone acetate and prednisolone in patients with prostate cancer. The study reported clinically and statistically significant improvements for abiraterone acetate with prednisolone to life-long ADT compared to life-long ADT alone. Separate analysis for metastatic and nonmetastatic patients was recommended to be conducted by the STAMPEDE Trial Steering Committee. 

The STAMPEDE extended analysis presents the long-term results of metastatic patients in the STAMPEDE “abiraterone comparison” with an increase in median follow-up to 73 months and the number of deaths by >50%. A total of 1003 patients with prostate cancer (both, newly diagnosed or relapsing) were randomised (1:1) to receive SOC (Standard-of-care) or SOC+AAP (abiraterone acetate, 1000 mg + prednisolone, 5 mg) until disease progression. Patients were classified into low-risk patients and high-risk patients as per the criteria defined by the LATITUDE trial where high-risk patients included those with at least two ≥3 bone metastases, visceral metastasis, and Gleason score ≥8.

The median age of all patients was 67 years; 94% were newly diagnosed; the metastatic disease risk group had 47% with high-risk, 43% low-risk, and 9% unclassified; median PSA levels were 97 ng/mL. A total of 88% patients had bone metastasis and 29% had distant lymph node metastasis. 

During the 6.1-year median follow-up, there were more deaths seen in the SOC group than in SOC+AAP treated (329 patients versus 244 patients). Consistent with this, median overall survival was significantly higher in the AAP-treated patients (79 months) than those treated with SOC (46 months, p<0.001). Failure-free survival, metastatic progression-free survival, progression-free survival, skeletal-related events, and disease-specific survival demonstrated significant improvement with SOC+AAP treatment versus the SOC alone treatment. Further, these effects of abiraterone plus prednisolone treatment were seen in both low-risk as well as high-risk patients.

Treatment Outcomes

SOC – Standard-of-care, AAP - abiraterone acetate and prednisone, CI – Confidence Interval

This study successfully demonstrated that the beneficial effects of abiraterone prednisolone combination reported in the previous STAMPEDE study were robust. The results strongly support the use of abiraterone for all patients on long-term hormone therapy for metastatic prostate cancer. 

Although abiraterone shows better efficacy than docetaxel (widely used SOC for prostate cancer), the costs of abiraterone are much higher than docetaxel. With abiraterone patent expiry in coming years, the costs of abiraterone treatment are expected to fall. 

The results of this study can then be meaningful for taking clinical decisions as substantial benefits of upfront targeting of the androgen receptor pathway using abiraterone acetate are evident in all men diagnosed with hormone-sensitive metastatic prostate cancer, irrespective of the metastatic disease risk group.³

Reference:

1. Prostate Cancer: Statistics [Internet]. Cancer Net. 2020. Available from: https://www.cancer.net/cancer-types/prostate-cancer/statistics

2. Perlmutter MA and Lepor H. Androgen deprivation therapy in the treatment of advanced prostate cancer. Rev Urol. 2007;9(Suppl 1):S3–8.

3. James et al. Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer 2022;151:422–34.