Discussion on SPARTAN: A Study of Apalutamide in Men with Non-Metastatic Castration-resistant Prostate Cancer - Thomas Keane
Dr. Thomas Keane reviews recent groundbreaking data presented at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium focusing on the much awaiting results of the SPARTAN trial.
Dr. Keane started by highlighting the SPARTAN Trial presentation by Dr. Eric Small. A Study of Apalutamide (ARN-509) in Men with Non-Metastatic Castration-resistant Prostate Cancer. Dr. Small provided the first presentation of the SPARTAN study results, a randomized double-blind controlled trial where 1,207 patients were recruited across all the institutions. Men were randomized in a 2:1 fashion to either apalutamide 240 mg daily + ADT or placebo + ADT.
During Dr. Small's presentation he reviews an important difference between the SPARTAN study design and PROSPER which is that once a patient developed metastases, they were offered secondary treatment and followed. The time from their first developed of metastases to the time they progressed on secondary therapy was defined as Progression-Free Survival-2, essentially a measure of time to progression as mCRPC.
Dr. Keane transitions into discussing a review of SPARTAN and PROSPER presented by Dr. Philip Kantoff which immediately followed the trial presentations at the 2018 ASCO GU meeting.
The introduction of androgen axis targeting agents, specifically enzalutamide (ENZA) and abiraterone (ABI), have revolutionized the field and the results of these trials were eagerly awaited.
Dr. Kantoff's overviews both the PROSPER study which specifically assesses ENZA in the cM0 CRPC setting, and SPARTAN which focused on apalutamide-ARN-509 (APA). Apalutamide is a next-generation competitive inhibitor of the androgen receptor under development for the treatment of patients with prostate cancer but perhaps with greater potency and reduced CNS effects. While the phase II results of APA in this setting were promising, demonstrating ≥50% PSA decline at 12 weeks in 89% of patients, median (time to PSA progression) TTPP of 24.0 mo (95% confidence interval [CI], 16.3 mo-not reached [NR]) and median MFS was NR (95% CI, 33.4 mo-NR).
Some important questions were raised during his presentation. While these two studies are strongly positive, he highlights the fact that these are asymptomatic non-metastatic patients, and therefore the burden of treatment may be higher than in mCRPC patients. The burden of proof must therefore be much higher.
Thomas E. Keane, MBBCh, FRCSI, FACS
Dr. Philip Kantoff is the Chairman of Medicine at Memorial Sloan Kettering Cancer Center and Professor of Medicine at the Weill Cornell Medical College. He is also the incumbent George J. Bosl Chair in Medicine. Dr. Kantoff oversees the clinical care, translational and clinical research of almost 400 faculty members in the Department of Medicine. He ensures the mentorship of fellows and junior faculty and cares for patients with prostate cancer. Dr. Kantoff’s laboratory- based research is devoted principally to the genetics and genetic epidemiology of prostate cancer, resistance to androgen deprivation therapy and the discovery of new biomarkers as potential prognostic and therapeutic targets. He lectures widely on both his research and the care of patients with these malignancies.
First Presentation - SPARTAN: A Study of Apalutamide (ARN-509) in Men with Non-Metastatic Castration-resistant Prostate Cancer
First Presentation - PROSPER: Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)
Philip Kantoff Review of First Presentation: SPARTAN and PROSPER of First Presentation: SPARTAN and PROSPER
FDA Approves Apalutamide, First Treatment for Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)