TY - JOUR
T1 - Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN
AU - Saad, Fred
AU - Small, Eric J.
AU - Feng, Felix Y.
AU - Graff, Julie N.
AU - Olmos, David
AU - Hadaschik, Boris A.
AU - Oudard, Stéphane
AU - Londhe, Anil
AU - Bhaumik, Amitabha
AU - Lopez-Gitlitz, Angela
AU - Thomas, Shibu
AU - Mundle, Suneel D.
AU - Chowdhury, Simon
AU - Smith, Matthew R.
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2022/2
Y1 - 2022/2
N2 - Background: Apalutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS), overall survival (OS), and time to prostate-specific antigen (PSA) progression in the placebo-controlled SPARTAN study of high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). Objective: To assess the relationships between PSA kinetics, outcomes, and molecular subtypes in SPARTAN. Design, setting, and participants: The authors conducted a post hoc analysis of nmCRPC patients randomized to receive apalutamide (n = 806) or placebo (n = 401) plus ADT and a subset stratified by molecular classifiers. Intervention: Apalutamide 240 mg/d. Outcome measurements and statistical analysis: The association between PSA kinetics and MFS, OS, time to PSA progression, and molecular subtypes was evaluated using the landmark analysis and Kaplan-Meier methods. Results and limitations: By 3 mo, PSA decreased in most apalutamide-treated patients and increased in most placebo-treated patients. After apalutamide, the median time to PSA nadir, confirmed ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml were 7.4, 1.0, 1.9, and 2.8 mo, respectively. By 6 mo, 90%, 57%, and 32% of apalutamide patients had ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml, respectively, while only 1.5% of placebo patients experienced ≥50% PSA reduction. PSA reductions were observed within 3 mo and up to 12 mo of apalutamide treatment, and were similar across molecular subtypes. Deep PSA responses (≥90% PSA reduction or PSA ≤0.2 ng/ml) at landmark 6-mo apalutamide treatment were significantly associated with improved time to PSA progression (hazard ratio {HR} [95% confidence interval {CI}] 0.25 [0.18–0.33] or 0.13 [0.08–0.21]), MFS (0.41 [0.29–0.57] or 0.3 [0.19–0.47]), and OS (0.45 [0.35–0.59] or 0.26 [0.18–0.38]; p < 0.001 for all). Conclusions: Apalutamide plus ADT produced rapid, deep, and durable PSA responses by 6-mo treatment regardless of assessed molecular prognostic markers. An early PSA response with apalutamide was associated with clinical benefits, supporting prognostic value of PSA monitoring. Patient summary: In this report, we describe how prostate-specific antigen (PSA) levels relate to outcomes in patients with nonmetastatic castration-resistant prostate cancer treated with apalutamide plus androgen deprivation therapy (ADT). We found that treatment with apalutamide plus ADT resulted in rapid, deep, and durable PSA responses in the majority of patients, including those with high-risk molecular subtypes, which were associated with improved survival.
AB - Background: Apalutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS), overall survival (OS), and time to prostate-specific antigen (PSA) progression in the placebo-controlled SPARTAN study of high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). Objective: To assess the relationships between PSA kinetics, outcomes, and molecular subtypes in SPARTAN. Design, setting, and participants: The authors conducted a post hoc analysis of nmCRPC patients randomized to receive apalutamide (n = 806) or placebo (n = 401) plus ADT and a subset stratified by molecular classifiers. Intervention: Apalutamide 240 mg/d. Outcome measurements and statistical analysis: The association between PSA kinetics and MFS, OS, time to PSA progression, and molecular subtypes was evaluated using the landmark analysis and Kaplan-Meier methods. Results and limitations: By 3 mo, PSA decreased in most apalutamide-treated patients and increased in most placebo-treated patients. After apalutamide, the median time to PSA nadir, confirmed ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml were 7.4, 1.0, 1.9, and 2.8 mo, respectively. By 6 mo, 90%, 57%, and 32% of apalutamide patients had ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml, respectively, while only 1.5% of placebo patients experienced ≥50% PSA reduction. PSA reductions were observed within 3 mo and up to 12 mo of apalutamide treatment, and were similar across molecular subtypes. Deep PSA responses (≥90% PSA reduction or PSA ≤0.2 ng/ml) at landmark 6-mo apalutamide treatment were significantly associated with improved time to PSA progression (hazard ratio {HR} [95% confidence interval {CI}] 0.25 [0.18–0.33] or 0.13 [0.08–0.21]), MFS (0.41 [0.29–0.57] or 0.3 [0.19–0.47]), and OS (0.45 [0.35–0.59] or 0.26 [0.18–0.38]; p < 0.001 for all). Conclusions: Apalutamide plus ADT produced rapid, deep, and durable PSA responses by 6-mo treatment regardless of assessed molecular prognostic markers. An early PSA response with apalutamide was associated with clinical benefits, supporting prognostic value of PSA monitoring. Patient summary: In this report, we describe how prostate-specific antigen (PSA) levels relate to outcomes in patients with nonmetastatic castration-resistant prostate cancer treated with apalutamide plus androgen deprivation therapy (ADT). We found that treatment with apalutamide plus ADT resulted in rapid, deep, and durable PSA responses in the majority of patients, including those with high-risk molecular subtypes, which were associated with improved survival.
KW - Androgen antagonists
KW - Nonmetastatic castration-resistant prostate cancer
KW - Prostate-specific antigen kinetics
KW - Prostatic neoplasm
UR - http://www.scopus.com/inward/record.url?scp=85121247839&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121247839&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2021.11.020
DO - 10.1016/j.eururo.2021.11.020
M3 - Article
C2 - 34916086
AN - SCOPUS:85121247839
SN - 0302-2838
VL - 81
SP - 184
EP - 192
JO - European Urology
JF - European Urology
IS - 2
ER -