SPARTAN Study Design

SPARTAN was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ERLEADA® + ADT vs placebo + ADT in patients with non-metastatic castration-resistant prostate cancer (nmCRPC)1-3

PSA results were blinded and were not used for treatment discontinuation.

Patients in SPARTAN had a PSA doubling time ≤10 months and serum testosterone levels <50 ng/dL. All patients in the SPARTAN trial received a concomitant GnRH analog or had a bilateral orchiectomy. All patients enrolled were confirmed to be non-metastatic by blinded central imaging review.* Patients with a history of seizure, predisposing factors for seizure, or receiving drugs known to decrease the seizure threshold or to induce seizure were excluded.1,2

*In the SPARTAN study, conventional imaging (technetium-9t9m bone scans and CT scans) was used to confirm that patients were non-metastatic at screening for inclusion. Patients with pelvic lymph nodes <2 cm in short axis (N1) located below the iliac bifurcation at screening were allowed in the study.3

 

Selected baseline patient characteristics1-3

Median age 74 years (range: 48 to 97 years)
Median time from initial diagnosis of prostate cancer to randomization 7.9 years (range: 0.3 to 30.4 years)
Prior surgery or radiation therapy for prostate cancer 77%
Prior treatment with a first-generation androgen receptor inhibitor 73%
Bicalutamide 69%
Flutamide 10%
Median PSA 7.8 ng/mL (range: 0.1 to 294.8 ng/mL)
Gleason score ≥7 at initial diagnosis 78%
Local or regional nodal disease (N1M0) 16%

Approximately 1 in 6patientsin SPARTAN had local or regional lymph node metastases at baseline3

Primary endpoint in SPARTAN: metastasis-free survival (MFS)

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 first1

Secondary endpoints in SPARTAN3

  • Time to metastasis
  • Progression-free survival
  • Time to symptomatic progression
  • Overall survival
  • Time to initiation of cytotoxic chemotherapy

Selected exploratory endpoints in SPARTAN3

  • Time to PSA progression
  • Health-related quality of life based on patient-reported outcomes (FACT-P and EQ-5D-3L)

Timeline of the SPARTAN study4

SPARTAN has the longest follow-up period of the registration trials that supported indications for the treatment of nmCRPC4-6

October 14, 2013

First patient randomized

SPARTAN Trial Begins

May 19, 2017

Clinical cutoff date

Primary Analysis

Median follow-up time 20.3 months

19% of patients in the placebo + ADT arm crossed over to receive ERLEADA® + ADT when the study was unblinded at the primary analysis.

Overall survival data were immature at this time.

February 1, 2020

Clinical cutoff date

Final Analysis

Median follow-up time: 52.0 months

At the time of the final analysis, 30% of patients originally randomized to the ERLEADA® + ADT arm were continuing to receive treatment with ERLEADA® + ADT.

Prespecified analysis of overall survival was conducted.

Patients receiving ERLEADA® + ADT stayed on therapy approximately 3 times longer than those receiving placebo + ADT4

Median Duration of Exposure at the Final Analysis4

Median Duration of Exposure at the Final Analysis

ADT = androgen deprivation therapy; CT = computed tomography; EQ-5D-3L = EuroQol 5-dimension, 3-level questionnaire;FACT-P = Functional Assessment of Cancer Therapy–Prostate; GnRH = gonadotropin-releasing hormone; PSA = prostate-specific antigen; SPARTAN = Selective Prostate Androgen Receptor Targeting with ARN-509.

References

1. ERLEADA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.

2. 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.

3. 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.

4. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. Eur Urol. 2021;79(1):150-158.

5. Sternberg CN, Fizazi K, Saad F, et al; PROSPER Investigators. Enzalutamide and survival in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2020;382(23):2197-2206.

6. Fizazi K, Shore N, Tammela TL, et al; ARAMIS Investigators. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049.