Eric J. Small, MD
Apalutamide (Erleada) lowered the risk of PSA progression by 94% in patients with nonmetastatic castration-resistant prostate cancer (CRPC), according to a posthoc analysis from the phase III SPARTAN trial presented at the 2018 American Urological Association (AUA) Annual Meeting.1
The median time to PSA progression was not reached in the apalutamide arm compared with 3.71 months in the placebo group (HR, 0.064; 95% CI, 0.052-0.080; P
<.0001). A separate retrospective cohort study presented at AUA underscored the significance of these apalutamide data by confirming prior observations of the link between faster PSA doubling time (PSADT) and poorer metastasis-free survival (MFS) and overall survival (OS).2
“Patients with nonmetastatic castration-resistant prostate cancer are at risk for metastases and mortality. In these patients, PSA doubling time is an important predictor of outcomes, including time to developing metastases or symptoms from their cancer,” Eric Small, MD, co-principal investigator of the SPARTAN study, said in a statement.
“This analysis further underscores the efficacy of apalutamide therapy and helps us understand how PSA changes in these patients are associated with clinical outcomes,” added Small, who is a professor of Medicine, chief of the Division of Hematology and Oncology, and deputy director of the Helen Diller Comprehensive Cancer Center at the University of California, San Francisco.
In February 2018, the FDA approved apalutamide for the treatment of patients with nonmetastatic CRPC, based on MFS data from the SPARTAN trial. The median MFS was 40.5 months in the apalutamide arm versus 16.2 months in the placebo arm (HR, 0.28; 95% CI, 0.23-0.35; P
The SPARTAN trial evaluated the safety and efficacy of apalutamide versus placebo in 1207 patients with nonmetastatic CRPC and a rapidly rising PSA level despite receiving continuous androgen deprivation therapy. Nonmetastatic status was determined by a negative bone scan, as well as a negative CT of the pelvis, abdomen, chest, and brain. Patients were required to have a PSA doubling time of ≤10 months.
Patients were randomized in a 2:1 ratio to 240 mg of apalutamide daily (n = 806) or placebo (n = 401). The median baseline PSA was 7.78 and 7.96 ng/mL in the 2 arms, respectively. The average baseline PSA doubling time was less than 5 months in both arms at 4.4 versus 4.5 months in the apalutamide versus placebo arms, respectively. Patients who developed metastases were allowed to receive abiraterone acetate (Zytiga) plus prednisone.
Beyond the primary MFS endpoint, secondary endpoints included time to metastasis, progression-free survival, time to symptomatic progression, and OS. For patients who developed metastases, the researchers also evaluated the time between randomization to first treatment for metastatic CRPC and subsequent progression.
According to the posthoc data presented at AUA, a confirmed PSA response was reported for 90% of the apalutamide arm versus 2% of the placebo arm (relative risk, 40.09; 95% CI, 20.99-76.58; P
<.0001). Among patients receiving apalutamide, the median time to PSA response was 29 days (range, 8-310).
At 12 weeks following randomization, the median PSA in the apalutamide group deceased by 90% compared with a 40% increase in patients receiving placebo. Additionally, 66% of patients in the apalutamide arm achieved a 90% maximum decline in PSA from baseline at any time point on the trial, compared with only 1% in the placebo group.
The retrospective analysis of PSADT presented at AUA used data from 84,479 prostate cancer patients from the Optum integrated electronic health records and claims database accrued between 2007 and 2017. Patients were considered high risk if they had a PSADT ≤10 months and low risk if their PSADT was >10 months.
Surgical and/or medical castration was administered to 15,431 patients. Among this group, 947 developed nonmetastatic CRPC, with 504 meeting criteria for continuous medical castration. The median patient age was 78.0 years at the onset of nonmetastatic CRPC.
PSADT was evaluable in 393 patients, of whom 38.2% (n = 150) were high risk and 61.8% (n = 243) were low risk. The median MFS was 15.2 versus 30.5 months in the high- versus low-risk populations, respectively (P
<.0001). The median OS was 36.0 versus 57.6 months, respectively (P
- Small EJ, Lee JY, Lopez-Gitlitz A, et al. Prostate-specific antigen (PSA) outcomes in patients (PTS) with nonmetastatic castration-resistant prostate cancer (NMCRPC) treated with apalutamide (APA): results from phase 3 SPARTAN study. Presented at: AUA Annual Meeting; May 18-21, 2018; San Francisco, CA. Abstract PD10-11.
- Saad F, Mehra M, Small EJ, et al. A population-based study of the association of prostate-specific antigen doubling time (PSADT) with metastasis-free survival (MFS) and overall survival (OS) in nonmetastatic castration-resistant prostate cancer (NMCRPC) patients (PTS). Presented at: AUA Annual Meeting; May 18-21, 2018; San Francisco, CA. Abstract PD10-04.