Efficacy in nmCRPC
Among all AR inhibitors FDA approved to treat nmCRPC:
ERLEADA® is the FIRST AND ONLY to deliver a 2-year improvement in median MFS
Primary endpoint in the SPARTAN study:
Metastasis-Free Survival (MFS)*1
Consistent results in metastasis-free survival (MFS) were observed across patient subgroups, including1:
- PSA doubling time (≤6 months or >6 months)
- Use of a prior bone-sparing agent (yes or no)
- Locoregional disease (N0 or N1)
*Metastasis-free survival was defined as the time from randomization to the time of first evidence of blinded independent central review-confirmed distant metastasis, defined as new bone or soft tissue lesions or enlarged lymph nodes above the iliac bifurcation, or death due to any cause, whichever occurred first.1
ERLEADA® improved median overall survival by 14 months
ERLEADA® is the FIRST AND ONLY therapy to improve median overall survival by more than 1 year in nmCRPC
Secondary endpoint in the SPARTAN study:
Overall Survival†1
Median follow-up time was 52.0 months.2
†Overall survival was defined as the time from randomization to the date of death due to any cause.3
Additional secondary endpoints favored the ERLEADA® + ADT arm1
‡Time to metastasis was defined as the time from randomization to the time of the scan that showed first evidence of blinded independent central review-confirmed radiographically detectable bone or soft tissue distant metastasis.3,4
§Progression-free survival was defined as the time from randomization to first documentation of blinded independent central review-confirmed radiographic progressive disease (local or distant) or death due to any cause, whichever occurred first.3,4
ERLEADA® significantly delayed chemotherapy initiation
ERLEADA® + ADT reduced the risk of initiation of cytotoxic chemotherapy by 37% vs placebo + ADT1
Secondary endpoint in the SPARTAN study:
Time to Initiation of Cytotoxic Chemotherapy¶2
¶Time to initiation of cytotoxic chemotherapy was defined as the time from randomization to documentation of a new cytotoxic chemotherapy being administered to the patient.3
Secondary endpoint:
The metastasis-free survival (MFS) outcome was supported by a statistically significant improvement in time to symptomatic progression4
Time to symptomatic progression was defined as the time from randomization to documentation of any of the following (whichever occurred earlier)3,4
- Development of a skeletal-related event: pathologic fracture, spinal cord compression, or need for surgical intervention or radiation therapy to the bone
- Pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anticancer therapy
- Development of clinically significant symptoms due to locoregional tumor progression requiring surgical intervention or radiation therapy
Examples of symptomatic progression evaluated in the SPARTAN study:
Spinal cord compression
The need for surgical intervention
The need for radiation therapy
Time to symptomatic progression is not reported in the ERLEADA® Prescribing Information.
Exploratory endpoint in the SPARTAN study:
Time to PSA progression: ERLEADA® + ADT vs placebo + ADT2
Time to PSA Progression#2
PSA response
38% of patients in the ERLEADA® + ADT arm achieved a confirmed PSA level ≤0.2 ng/mL vs no patients in the placebo + ADT arm.2
#Time to PSA progression was defined as the time from randomization to PSA progression, according to Prostate Cancer Working Group 2 (PCWG2) criteria. For patients who experienced a decline in PSA from baseline, PSA progression was defined as the first PSA increase that was ≥25% and ≥2 ng/mL above the nadir, which was confirmed by a second value obtained 3 or more weeks later. For patients who did not experience a decline in PSA from baseline, PSA progression was defined as a PSA increase that was ≥25% and ≥2 ng/mL above the baseline value after 12 weeks.4,6
Time to PSA progression and PSA response rate are not reported in product labeling because they are not reliable surrogates for overall survival. PSA evaluation should be viewed in the context of patient management and the overall physical condition and clinical course of the patient.7
ADT = androgen deprivation therapy; AR = androgen receptor; CI = confidence interval; FDA = US Food and Drug Administration;HR = hazard ratio; nmCRPC = non-metastatic castration-resistant prostate cancer; PSA = prostate-specific antigen; SPARTAN = Selective Prostate Androgen Receptor Targeting with ARN-509.
References
1. ERLEADA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
2. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. Eur Urol. 2021;79(1):150-158.
3. U.S. Food and Drug Administration. Drug Approval Package: ERLEADA® (apalutamide). SPARTAN Clinical Study Report. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/Erleada_210951_toc.cfm. Accessed March 3, 2021.
4. Smith MR, Saad F, Chowdhury S, et al; for the SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378(15):1408-1418.
5. Smith MR, Saad F, Rathkopf DE, et al. Relationship of time to metastasis (TTM) and site of metastases in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): results from the phase 3 SPARTAN trial [abstract 5033]. J Clin Oncol. 2018;36(15_suppl).
6. Scher HI, Halabi S, Tannock I, et al; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26(7):1148-1159.
7. Crawford ED, Bennett CL, Andriole GL, Garnick MB, Petrylak DP. The utility of prostate-specific antigen in the management of advanced prostate cancer. BJU Int. 2013;112(5):548-560.
