Adding abiraterone and prednisolone to standard therapy significantly improved survival in multiple groups of prostate cancer patients compared to standard therapy alone, according to data from a pair of studies presented at the European Society for Medical Oncology (ESMO) Congress 2021 (Abstracts LBA4 and LBA5).
In the phase 3 STAMPEDE trial, researchers randomly assigned 1,974 men with high-risk, non-metastatic prostate cancer to the standard androgen deprivation therapy (ADT) or to a combination of abiraterone plus prednisolone (AAP) added to ADT with or without enzalutamide. Patients were treated for two years at 113 sites in the United Kingdom and Switzerland. The median age of the patients was 68, and baseline clinical information was similar between the groups.
At six years’ follow-up, men in the standard treatment plus AAP group had a significantly higher rate of metastasis-free survival than those just on standard care (82% versus 69%) and of overall survival (86% versus 77%). The effect was similar across subgroups and regardless of whether patients also received enzalutamide.
The trial addresses a need for better treatments for men with non-metastatic prostate cancer, said study leader Gerhardt Attard, MD, PhD, of University College London Cancer Institute during his ESMO presentation. “The magnitude of benefit is much greater than was previously estimated,” he said of the survival advantage derived from adding AAP to ADT.
In a second study, the phase 3 PEACE-1 trial, the addition of AAP to standard care improved both overall survival and radiographic progression-free survival in men with de novo metastatic, castration-sensitive prostate cancer.
It was previously known that adding docetaxel or an androgen signaling inhibitor like abiraterone to ADT improved overall survival in this group of patients. It was also known that radiation to the primary tumor in a subgroup of patients with limited disease improved survival when added to ADT. However, it was unclear whether it would help to add more than one of these treatments to ADT.
“Until now, it was unknown whether multiple treatments should be combined in men with prostate cancer,” and specifically whether just one or both of AAP and docetaxel should be added to ADT to achieve the best outcomes, said Karim Fizazi, MD, PhD, of the University of Paris-Saclay in Villejuif, France, during his presentation on the study findings.
Dr. Fizazi and his colleagues randomly assigned 1,173 men with de novo metastatic, castration-sensitive prostate cancer to standard care, standard care plus AAP, standard care plus radiotherapy, or standard care plus AAP and radiotherapy. Standard care consisted of ADT plus or minus docetaxel.
Adding AAP to ADT plus docetaxel improved median radiographic progression-free survival by 2.5 years, Dr. Fizazi said. In addition, over a median follow-up period of 4.4 years, “adding abiraterone reduced the risk of death by 25%,” he noted. Dr. Fizazi added that a longer period of follow-up will be needed to assess the role of radiation therapy.
Eleni Efstathiou, MD, PhD, of Houston Methodist Cancer Center served as a discussant for both studies. The STAMPEDE trial design was “as close to everyday practice as you can have it,” Dr. Efstathiou said, adding that finding better ways to treat high-risk, locally advanced prostate cancer has been “truly an unmet need.”
The STAMPEDE study findings were limited by the lack of data on long-term complications and on longer-term treatment durations, Dr. Attard said. However, the results suggest that adding AAP to ADT should now be considered a new standard of care for patients with high-risk non-metastatic prostate cancer, he said.
The PEACE-1 trial showed the value of triplet therapy with ADT, docetaxel, and AAP, with evidence that the addition of AAP to standard care had a clinically meaningful overall survival benefit with and without docetaxel, Dr. Efstathiou noted.
According to Dr. Efstathiou, the take-home message from the studies is that adding abiraterone to standard care is a practice-changing strategy, especially if given early.
The STAMPEDE study was funded by Cancer Research UK, the Medical Research Council, Astellas, and Janssen. Dr. Attard disclosed relationships with multiple companies included Astellas and Janssen.
The PEACE-1 study was supported by Janssen Pharmaceutical NV, Ipsen, Sanofi, and PHRC. Dr. Fizazi disclosed relationships with multiple companies including Janssen.
Dr. Efstathiou disclosed relationships with multiple companies including Janssen, Sanofi-Genzyme, Astellas, and Ortho Pharma.
