Two years of abiraterone acetate (Zytiga) plus prednisone added to androgen-deprivation therapy (ADT) improved metastasis-free survival and overall survival compared with ADT alone in men with nonmetastatic castration-sensitive prostate cancer, whereas the addition of enzalutamide (Xtandi) to ADT had no benefit, and much greater toxicity. These were the main findings of a meta-analysis of 2 separate arms of the STAMPEDE clinical trial presented at the European Society for Medical Oncology Congress 2021.
The addition of abiraterone acetate plus prednisone significantly improved metastasis-free survival by 47% versus ADT alone (P <.001). Abiraterone acetate plus prednisone plus ADT also significantly improved overall survival by 40% compared with ADT alone: 147 deaths in the triple-drug regimen arm versus 236 deaths with ADT alone (P <.0001).
“These are headline results with excellent news for patients and physicians….Two years of AAP [abiraterone acetate plus prednisone]-based therapy significantly improves metastasis-free survival and overall survival in men with high-risk nonmetastatic prostate cancer starting androgen-deprivation therapy and should be considered a new standard of care,” stated lead investigator Gerhardt Attard, MD, PhD, FRCP, John Black Charitable Foundation Endowed Chair in Urological Cancer Research, University College London Cancer Institute, England. “The analysis of STAMPEDE also showed that adding enzalutamide to AAP increases toxicity but has no discernible effect on efficacy.”
To determine the role of abiraterone acetate plus prednisone and abiraterone acetate plus prednisone plus or minus enzalutamide added to ADT, investigators amended the reporting plan for STAMPEDE to assess patients with nonmetastatic and metastatic disease separately, and to perform a meta-analysis that included new data from 2 years of abiraterone acetate plus prednisone plus or minus enzalutamide. The analysis focused on patients with node-positive or high-risk, node-negative disease who were randomized to ADT alone versus ADT plus abiraterone acetate plus prednisone or ADT versus ADT plus abiraterone acetate plus prednisone plus enzalutamide.
The study included 1974 patients (median age, 68 years) with a median prostate-specific antigen of 34 ng/mL, and 39% had 1 positive lymph node. The median follow-up was 72 months.
The addition of abiraterone acetate plus prednisone to ADT improved metastasis-free survival by approximately 56% in the 2 randomization periods. Abiraterone acetate plus prednisone was of benefit across all prespecified subgroups: nodal status, age, World Health Organization performance status, aspirin use at baseline, and radiotherapy to the prostate as part of the planned treatment.
The overall survival was also significantly improved, by 40%, with the addition of abiraterone acetate plus prednisone (P = .92 × 10-7). The 6-year survival rate improved from 77% with ADT to 86% with abiraterone acetate plus prednisone plus ADT.
Secondary outcomes measures were also significantly improved by abiraterone acetate plus prednisone. The 6-year prostate-specific survival improved from 85% with ADT alone to 93% with abiraterone acetate plus prednisone plus ADT. Progression-free survival improved by 56% with the addition of abiraterone acetate plus prednisone.
The use of abiraterone acetate plus prednisone and enzalutamide increased the incidence of adverse events (AEs) compared with ADT alone. The most serious AEs were seen in the 3-drug regimen without ADT arm, with 4 deaths; 3 deaths were reported with abiraterone acetate plus prednisone; and no deaths were reported in the ADT-alone arm. Grade 4 AEs occurred in 12 patients in each of the ADT arms, in 17 patients in the abiraterone acetate plus prednisone arm, and in 23 patients in the abiraterone acetate plus prednisone plus enzalutamide arm.
“The STAMPEDE investigative group has an impressive track record in practice-changing contributions. Androgen receptor–signaling inhibition is now a key strategy in the treatment of metastatic prostate cancer,” said invited discussant Eleni Efstathiou, MD, PhD, GU Medical Oncology, M.D. Anderson Cancer Center, Houston, TX. “STAMPEDE is truly practice-changing and addresses unmet needs. The survival results are clinically meaningful. The treatments are accessible to the community, but we have to be very vigilant about monitoring,” she stated.