In a post hoc analysis of the phase III ARCHES and PROSPER trials reported in the Journal of Clinical Oncology, Armstrong et al found that radiographic progression (rPD) often occurred without prostate-specific antigen (PSA) rise in patients with advanced prostate cancer receiving the androgen receptor enzalutamide.
Study Details and Key Findings
Using data from 2,551 patients from the two trials, investigators analyzed the development of rPD without PSA rise or progression in metastatic hormone–sensitive prostate cancer (mHSPC) and nonmetastatic castration–resistant prostate cancer (nmCRPC).
In ARCHES, 3.5% and 8.5% of 574 patients with mHSPC who received enzalutamide plus androgen-deprivation therapy (ADT) had no PSA rise or PSA progression at rPD, respectively. Among 79 patients with rPD who received enzalutamide plus ADT, 25.3% had no PSA rise and 62.0% did not have PSA progression compared with 7.4% and 38.3% of 188 patients with rPD treated with ADT alone, respectively.
In PROSPER, 4.4% and 10.3% of 933 patients with nmCRPC treated with enzalutamide plus ADT had no PSA rise or PSA progression, respectively, at rPD. Among 187 patients with rPD who received enzalutamide plus ADT, 21.9% had no PSA rise and 51.3% did not meet PSA progression criteria compared with 3.6% and 18.8% of 224 patients treated with placebo/ADT, respectively.
In sensitivity analyses, patients in both groups in ARCHES who had rPD had significantly poorer overall survival vs those with no rPD, irrespective of PSA progression or PSA rise. In PROSPER, compared with no rPD, enzalutamide-treated patients with rPD had significantly shorter overall survival with or without PSA progression or PSA rise; in the placebo group, overall survival was significantly shorter only in patients with rPD without PSA progression.
The investigators concluded: “Given the frequent discordance and poor prognosis of imaging-based progression in the absence of PSA changes during enzalutamide treatment in mHSPC and nmCRPC, periodic surveillance using imaging is recommended.”
Andrew J. Armstrong, MD, ScM, FACP, of Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, North Carolina, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Pfizer Inc and Astellas Pharma Inc. For full disclosures of the study authors, visit ascopubs.org.
