Adding abiraterone acetate and prednisone or docetaxel and prednisone to long-term androgen deprivation therapy in patients with high-risk prostate cancer: both effective treatment options
Previous data from the large, multi-arm, randomized STAMPEDE trial demonstrated that adding abiraterone acetate + prednisone (AAP), or docetaxel + prednisone (DocP) to standard androgen deprivation therapy (ADT) both improved the survival as compared to ADT alone in patients with high-risk locally advanced or metastatic prostate cancer starting long-term ADT. During ESMO 2017 the results were presented of a direct comparison between ADT + AAP and ADT + DocP.
Long-term hormone therapy alone has been the standard of care for patients with high-risk locally advanced or metastatic prostate cancer since the 1940s. STAMPEDE is a platform protocol using a multi-arm, multi-stage design to efficiently investigate a number of new treatments versus SOC in patients with high-risk prostate cancer. It included men who were starting long-term hormonal therapy for the first time. As indicated above, the trial previously found that adding docetaxel + prednisone to ADT improved the overall survival (OS) (HR: 0.78), and that adding abiraterone acetate + prednisone also led to a significant improvement in OS compared to ADT alone (HR: 0.63).
The analysis presented at ESMO used prospectively collected data from the STAMPEDE trial to directly compare patients randomized to the docetaxel + prednisone (DocP) and abiraterone acetate + prednisone (AAP) research arms while both arms of the trial were recruiting. The randomizations overlapped between November 2011 and March 2013. This comparison included 566 patients, of whom 189 were randomized to receive DocP and 377 were randomized to receive AAP, both on top of standard of care ADT (with radiotherapy for some patients).
The analysis did not reveal a significant difference in OS between both arms (HR[95%CI]: 1.16[0.82-1.65]). When looking at the early outcome measures of failure-free survival (FFS) and progression-free survival (PFS) the HRs indicated a superior benefit of AAP over DocP (HR[95%CI] for PFS: 0.65[0.48-0.88]; p= 0.005; HR[95%CI] for FFS: 0.51[0.39-0.67]; p< 0.05). In addition to this, the estimates of treatment effect for late outcome measures of freedom from metastatic progression (HR[95%CI]: 0.77[0.57-1.03]) and freedom from symptomatic skeletal events (HR[95%CI]: 0.83[0.55-1.25]) also favored AAP, but the differences between treatment groups were not statistically significant for these endpoints.
In discussing these data, professor Nicholas James, Chief Investigator of STAMPEDE, indicated that the individual trials suggested that abiraterone acetate may have a larger effect on survival than docetaxel, but that this did not translate into a clear advantage in this study. In fact, both drugs provide a comparable survival advantage over SOC alone in men with high-risk prostate cancer beginning long-term hormone therapy. As such, starting with either drug is acceptable and choice may depend on availability.
Toxicity may also be a factor in opting for one of the two regimens. While there was no difference in the incidence of high-grade (≥grade 3) toxicities (50% for DocP versus 48% for AAP), the toxicity profiles were quite different in the 2 trials (e.g. DocP associated with more high-grade [febrile] neutropenia, while AAP induced more high-grade musculoskeletal and cardiovascular disorders). As such physicians will likely base their choice of therapy not only on availability, but also on the patient characteristics and their preferences.
Sydes M, Mason M, Spears M, et al. Adding abiraterone acetate plus prednisolone (AAP) or docetaxel for patients (pts) with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): directly randomised data from STAMPEDE (NCT00268476). Presented at ESMO 2017; Abstract LBA31_PR.