Efficacy in nmCRPC

Primary endpoint:

In patients with nmCRPC:

ERLEADA® + ADT improved median metastasis-free survival (MFS) by 2 YEARS vs placebo + ADT1

72% reduction in the risk of distant metastasis or death

HR=0.28; 95% CI: 0.23, 0.35; P<0.0001

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

At the time of the analysis, 60.9% of patients were still on ERLEADA® + ADT vs 29.9% of patients still on placebo + ADT2

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.2,3

Progression-free survival was defined as the time from randomization to first documentation of blinded independent central review-confirmed radiographic progressive disease or death due to any cause, whichever occurred first.2,3

Sites of metastasis§4

Patients with metastasis (%) ERLEADA®
+ ADT
(n=175)
Placebo
+ ADT
(n=191)
Bone 57% 52%
Nodal 30% 40%
Visceral 13% 8%

§As reported in a post hoc analysis of SPARTAN. In the SPARTAN study, 175 patients (22%) in the ERLEADA® + ADT arm and 191 patients (48%) in the placebo + ADT arm developed metastasis.1

Secondary endpoint:

The metastasis-free survival (MFS) outcome was supported by a statistically significant improvement in time to symptomatic progression1

Time to symptomatic progression was defined as the time from randomization to documentation of any of the following (whichever occurred earlier)2,3

  • 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:

A circular x-ray, showing the spinal cord being pinched by a lump

Spinal cord compression

A circular x-ray, showing a replaced hip joint

The need for surgical intervention

A circular photo of a M R I machine

The need for radiation therapy

 

SPARTAN Final Analysis

Final analysis data from the SPARTAN study are not currently reported in the Prescribing Information for ERLEADA®.

SPARTAN has the longest follow-up period of the registration trials that supported indications for the treatment of nmCRPC5-7

October 14, 2013

First patient randomized

SPARTAN Trial Begins

May 19, 2017

Clinical cutoff date

Primary Analysis

Median follow-up time: 20.3 months5

19% of patients in the placebo + ADT arm crossed over to receive ERLEADA® + ADT when the study was unblinded at the primary analysis.5

Overall survival data were immature at this time.1

February 1, 2020

Clinical cutoff date

Final Analysis

Median follow-up time: 52.0 months5

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.5

Prespecified analysis of overall survival was conducted.5

Patients receiving ERLEADA® + ADT stayed on therapy approximately 3 times longer than those receiving placebo + ADT5

Median Duration of Exposure at the Final Analysis5

Many patients who received ERLEADA® lived more than 1 year longer:

ERLEADA® + ADT improved median overall survival by 14 MONTHS vs placebo + ADT5

Secondary endpoint:

Overall Survival5

Median follow-up time was 52.0 months.5

Median overall survival for patients who took ERLEADA® + ADT was more than 6 years compared with 5 years for patients who took placebo + ADT5

ADT = androgen deprivation therapy; CI = confidence interval; 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; for the SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378(15):1408-1418.

3. U.S. Food and Drug Administration. Drug Approval Package: ERLEADA® (apalutamide). SPARTAN Clinical Study Report.. Accessed August 14, 2020.

4. 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).

5. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer [published online September 6, 2020]. Eur Urol. doi.org/10.1016/j.eururo.2020.08.011

6. 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.

7. Fizazi K, Shore ND, Tammela T, et al. Overall survival results of phase III ARAMIS study of darolutamide added to androgen deprivation therapy for non-metastatic castration-resistant prostate cancer. Poster presented at: ASCO Annual Meeting; May 29-31, 2020; Chicago, IL.