Efficacy in mCSPC
ERLEADA® is the FIRST AND ONLY AR inhibitor to report overall survival over ADT alone for patients with mCSPC in FDA-approved labeling
Dual primary endpoints:
OS results from the primary analysis of the TITAN study in patients with mCSPC:
ERLEADA® + ADT reduced the risk of death by 33% vs placebo + ADT1
Median follow-up time was 22.7 months.2
*Overall survival was defined as the time from randomization to the date of death from any cause.2
Dual primary endpoint from the primary analysis of the TITAN study:
ERLEADA® + ADT demonstrated superior rPFS vs placebo + ADT
ERLEADA® + ADT reduced the risk of radiographic progression or death by 52% vs placebo + ADT1
Median rPFS was not estimable with ERLEADA® + ADT vs 22.1 months with placebo + ADT1
Radiographic Progression-Free Survival (rPFS)†
At 2 years, 68.2% of patients in the ERLEADA® + ADT arm were alive and without radiographic progression vs 47.5% of patients in the placebo + ADT arm2
†rPFS was based on investigator assessment and was defined as time from randomization to radiographic disease progression or death. Radiographic disease progression was defined by identification of 2 or more new bone lesions on a bone scan with confirmation (Prostate Cancer Working Group 2 criteria) and/or progression in soft tissue disease.1
ERLEADA® demonstrated consistent results in these prespecified patient subgroups1
‡High volume of disease was defined as metastases involving the viscera with 1 bone lesion or the presence of 4 or more bone lesions, at least 1 of which must be in a bony structure beyond the vertebral column and pelvic bones.1
Secondary endpoint from the primary analysis of the TITAN study:
ERLEADA® significantly delayed chemotherapy initiation
ERLEADA® + ADT reduced the risk of initiation of cytotoxic chemotherapy by 61% vs placebo + ADT1
Time to Initiation of Cytotoxic Chemotherapy§2,3
§Time to cytotoxic chemotherapy was defined as the time from randomization to initiation of cytotoxic chemotherapy.2
Exploratory endpoint from the primary analysis of the TITAN study:
Time to PSA progression: ERLEADA® + ADT vs placebo + ADT2
Time to PSA ProgressionII2
PSA reached undetectable levels (<0.2 ng/mL) in 68.4% of patients in the ERLEADA® + ADT arm vs 28.7% of patients in the placebo + ADT arm.2
IITime 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.2,4
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.5
TITAN Final Analysis
Final analysis data from the TITAN study are not currently reported in the Prescribing Information for ERLEADA®.
Timeline of the TITAN Study6
December 15, 2015
First patient randomized
TITAN Trial Begins
November 23, 2018
Clinical cutoff date
Median follow-up time: 22.7 months
39.5% of patients in the placebo + ADT arm crossed over to receive ERLEADA® + ADT when the study was unblinded at the primary analysis.
First analysis of overall survival.
September 7, 2020
Clinical cutoff date
Median follow-up time: 44.0 months
At the time of the final analysis, 51% of patients originally randomized to the ERLEADA® + ADT arm were continuing to receive treatment with ERLEADA® + ADT.
Final analysis of overall survival.
Patients receiving ERLEADA® + ADT stayed on therapy nearly twice as long as those who received placebo + ADT6
Median Duration of Exposure at the Final Analysis6
Among all registration trials in mCSPC:
ERLEADA® is the FIRST AND ONLY AR inhibitor to achieve a 35% reduction in the risk of death vs ADT alone
Dual primary endpoint in the TITAN study:
Median follow-up time was 44.0 months.6
After nearly 4 years of median follow-up:
Consistent improvement in overall survival
was observed with ERLEADA® + ADT vs placebo + ADT across the following prespecified patient subgroups6:
- Disease volume (high vs low)‡
- Gleason score at diagnosis (≤7 vs >7)
¶TITAN final analysis data are not currently reported in the ERLEADA® Prescribing Information. The following TITAN primary analysis results are included in the ERLEADA® Prescribing Information: Median OS: NE vs NE; HR=0.67; 95% CI: 0.51, 0.89; P=0.0053.1
ADT = androgen deprivation therapy; AR = androgen receptor; CI = confidence interval; FDA = US Food and Drug Administration;HR = hazard ratio; mCSPC = metastatic castration-sensitive prostate cancer; NR = not reached; OS = overall survival; TITAN = Targeted Investigational Treatment Analysis of Novel Antiandrogen.
1. ERLEADA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
2. Chi KN, Agarwal N, Bjartell A, et al; for the TITAN Investigators. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13-24.
3. Data on file. Janssen Biotech, Inc.
4. 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.
5. 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.
6. Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study [published online April 29, 2021]. J Clin Oncol. doi.org/10.1200/JCO.20.03488