MUNICH – Men with metastatic hormone-naive prostate cancer may benefit from treatment with the combination of abiraterone (Zytiga), prednisolone, and androgen deprivation regardless of risk group or disease volume, STAMPEDE trialists contend.
Results of thetrials, published in 2017 in the New England Journal of Medicine, showed significant improvements in overall survival with abiraterone, androgen deprivation therapy (ADT) and either prednisone (in LATITUDE) or prednisolone (in STAMPEDE) compared with ADT alone.
Data from the LATITUDE trial were used to support approval by both the Food and Drug Administration and European Medicines Agency of abiraterone in combination with ADT and a glucocorticoid for the new indication of treatment of men with metastatic high-risk castration-sensitive prostate cancer.
“So where we stand, at the minute, in terms of guidance: the EAU [European Urology Association] and the NCCN [National Comprehensive Cancer Network] have suggested that we consider treatment for men with hormone-naive metastatic prostatic cancer, but in 2018 the FDA and EMA licensed the drug for high-risk disease, so there’s therefore an evolving uncertainty about what we should be doing in low-risk disease,” Alex Hoyle, MBChB, of Christie NHS Foundation Trust, Manchester, England, said on behalf of colleagues in the STAMPEDE trial group.
The problem is that there is no international consensus on what constitutes low-risk disease, Dr. Hoyle said at the European Society for Medical Oncology Congress.
For example, in the, risk was defined by volume, with high-risk patients defined as those with visceral metastases and/or four or more bone metastases with one or more outside the vertebral column or pelvis. In contrast, the LATITUDE investigators defined high-risk patients as those with two or more high-risk features, including three or more bone metastases, visceral metastases, and/or a Gleason score of 8 or more.
To determine whether men with low-risk disease could also benefit from the combination, Dr. Hoyle and colleagues performed a retrospective analysis of the STAMPEDE trial, using staging scans to stratify patients with M1 disease into either high- or low-risk categories according to the LATITUDE risk criteria. The reviewers were blinded to the treatment arm for each patient. They also performed a secondary differential analysis by tumor volume according to the CHAARTED criteria.
The investigators then retrospectively reviewed outcomes for 901 evaluable patients, median age 67 years, with a median PSA of 96 ng/mL, followed for a median of 42 months. The sample included 428 patients determined to have low-risk disease, and 473 determined to have high-risk disease.
Overall survival (OS), the primary endpoint, was significantly better for patients treated with the combination vs. ADT alone in both high- and low-risk groups. The 3-year OS in high-risk patients treated with the abiraterone/prednisolone/ADT was 64.7% compared with 45% for patients treated with AD alone, an absolute difference of 19.7% that translated into a hazard ratio (HR) for death of 0.54 (P less than .001).
For patients in the low-risk group, 3-year OS was 82.4% with the combination vs. 78% with ADT alone, an absolute difference of 4.4%, translating into an HR of 0.66 (P = .041).
Three-year prostate cancer-specific survival, a secondary endpoint, was better with abiraterone in the high-risk (67% vs. 47.9%, HR 0.57, P less than .001) and low-risk (88.7% vs. 81.6%, HR 0.51, P = .008) populations.
The results were even more pronounced in favor of the abiraterone combination for the secondary endpoint of failure-free survival (FFS) in both groups, with 45.1% of high-risk patients on abiraterone having no biochemical failure at 3 years vs. 12.2% for those treated with ADT alone (HR 0.48, P less than .001). The respective FFS rates in the low-risk group were 80.8% vs. 56.4% (HR 0.66, P = .041).
ADT was superior in analyses of skeletal related event-free survival (HR 0.48 for high risk and 0.31 for low risk, P less than .001 for both comparisons), and metastasis progression-free survival (HR 0.54, P less than .001 for high risk, HR 0.66, P = .041 for low risk).
An exploratory analysis using the CHAARTED risk criteria showed similar results, with the combination significantly better in every category except prostate cancer–specific survival in patients with low-volume disease, although here, too, there was a clear trend favoring abiraterone.
“Abiraterone plus prednisolone in addition to ADT improves survival endpoints in metastatic hormone-naive prostate cancer,” Dr. Hoyle said.
Invited discussant Karim Fizazi, MD, PhD, of Gustave Roussy Cancer Institute at the University of Paris-Sud, France, said that the study, despite some limitations, was very important.
“For patients with high-risk de novo disease, until today we’ve had two standards of care: castration plus abiraterone or castration plus docetaxel. For patients with low risk, that was strongly debated – either castration alone or castration plus docetaxel. After this publication, I think it’s fair to say that for patients with high-risk disease the role of abiraterone is being strengthened, while for patients with low-risk disease, ADT plus abiraterone probably is going to become the new standard,” he said.
The STAMPEDE trial is supported by the Medical Research Council of the United Kingdom, the Salford Royal and the Christie NHS Foundation trusts, and Manchester Cancer Research Centre. Dr. Hoyle reported having no conflicts of interest. Dr. Fizazi reported advisory board participation and/or honoraria from Amgen, Astellas, AstraZeneca, Bayer, Clovis, CureVac, Essa, Genentech, Janssen, MSD, Orion, and Sanofi.
SOURCE: Hoyle AP et al. ESMO 2018. Abstract LBA4.