The results of SPARTAN, the study in which patients were treated with apalutamide (APA), demonstrated a 24 month MFS benefit and a trend towards OS benefit (interim analysis). Full results of the initial presentation: First Presentation - SPARTAN: A Study of Apalutamide (ARN-509) in Men with Non-Metastatic Castration-resistant Prostate Cancer
In this abstract by the SPARTAN trial collaborators, the focus shifts to prostate-specific antigen (PSA) related endpoints. Again, while the primary outcome of the original paper was MFS (metastasis-free survival), secondary outcomes included time to PSA progression, progression-free survival, OS, secondary PFS (on subsequent therapies), and adverse event profile. PSA was assessed by a central laboratory and blinded to the patients and investigators – they were collected at day 1, every 4 weeks (months 1-6), every 8 weeks (months 7-13), and every 16 weeks thereafter. PSA response was defined as a ≥ 50% decline from baseline and confirmed on a subsequent measurement at least 4 weeks later. Time to PSA progression was defined as the time from randomization to PSA progression according to Prostate Cancer Working Group 2 criteria.
The patients in both arms were well-balanced. Full inclusion criteria and patient stratification during randomization can be found on our initial coverage. A total of 1207 patients were randomized in a 2:1 APA/placebo (PBO) fashion.
PSA specific outcomes:
1. Confirmed PSA response was observed in 90% and 2% of pts in the APA and PBO groups, respectively (RR = 40.09; 95% CI, 20.99-76.58; p < 0.0001)
2. The median time to PSA response was 29 (range, 8-310) days in the APA group – less than 1 month!
3. At 12 weeks after randomization, median PSA decreased by 90% in the APA group and increased by 40% in the PBO group
4. A ≥ 90% maximum decline in PSA from baseline at any time on study was observed in 66% and 1% of pts in the APA and PBO groups, respectively.
- PSA levels < 0.20 ng/dL were reached in 40% of patients in the APA arm
- PSA levels < 0.02 ng/dL were reached in 13% of patients in the APA arm
5. APA significantly decreased the risk of PSA progression by 94% compared with PBO (not reached vs 3.71 mos; HR = 0.064; 95% CI, 0.052-0.080; p < 0.0001).
6. Baseline PSA doubling time predicted MFS, risk of symptomatic progression, PFS2.
7. PSA decline was also associated with other outcomes
- Associated with MFS
- Patients with PSA <0.02 did the best! As expected (HR 0.05)
- Patients with >90% decline (HR 0.30)
- Patients with >50% decline (HR 0.61)
- Associated with Symptomatic Progression
- Associated with PFS2
Overall, as described previously, the patients tolerated APA very well – discontinuation rates were similar in both groups (10.7% APA, 6.3% placebo).
In this study, the description of apalutamide’s PSA effect is complementary to its primary outcome. This detailed abstract focusing on the PSA response to apalutamide highlights the potent effect APA has on the AR axis.
What is even more important is that PSA was blinded to the patients and investigators. Its relationship to OS outcomes will be critical.
Presented by: Eric J. Small, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Co-Authors: Ji Youl Lee, Angela Lopez-Gitlitz, Fred Saad, Brendan Rooney, Boris A. Hadaschik, Hiroji Uemura, Youyi Shu, Margaret Yu, Matthew R. Smith
Author Affiliation: Multi-institutional, International – SPARTAN Trial Group
1. C Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. doi: 10.1056/NEJMoa1503747. Epub 2015 Aug 5.doi
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, | twitter: @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
Further Related Content:
Eric J. Small, MD 2018 AUA Presentation Patient Reported Outcomes in SPARTAN, a Phase 3, Double-Blind, Randomized Study of Apalutamide plus ADT vs placebo plus ADT in Men with nmCRPC
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