Frequently Asked Questions
ERLEADA® is indicated for the treatment of patients with1
- Metastatic castration-sensitive prostate cancer (mCSPC)
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- ERLEADA® is an androgen receptor (AR) inhibitor1
- ERLEADA® binds directly to the ligand-binding domain of the AR, inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription1
- The recommended dose of ERLEADA® is 240 mg (four 60 mg tablets) administered orally once daily1
- Patients should also receive a GnRH analog concurrently or should have had a bilateral orchiectomy1
- If a patient experiences a ≥Grade 3 toxicity or an intolerable side effect, hold dosing until symptoms improve to ≤Grade 1 or original grade, and then resume at the same dose or a reduced dose (180 mg or 120 mg), if warranted1
The most common adverse reactions (≥10%) that occurred more frequently in the ERLEADA®-treated patients (≥2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.1
National Comprehensive Cancer Network® (NCCN®)2
Metastatic (M1) Castration-Naive Prostate Cancer
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) include apalutamide (ERLEADA®) with androgen deprivation* as a Category 1 Preferred treatment option for patients with metastatic (M1) castration-naive prostate cancer.†
Non-Metastatic (M0) Castration-Resistant Prostate Cancer
The NCCN Guidelines® include apalutamide (ERLEADA®) with continued androgen deprivation* as a Category 1 Preferred treatment option for patients with non-metastatic (M0)‡ CRPC and a PSA doubling time ≤10 months.
*Orchiectomy, LHRH agonist, or LHRH antagonist.
†The term “castration-naive” is used to define patients who are not on ADT at the time of progression. The NCCN Prostate Cancer Panel uses the term “castration-naive” even when patients have had neoadjuvant, concurrent, or adjuvant ADT as part of radiation therapy provided they have recovered testicular function.
‡Definition of non-metastatic (M0): Conventional imaging studies negative for distant metastases.
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Preferred intervention: Interventions that are based on superior efficacy, safety, and evidence, and, when appropriate, affordability.
To view the most recent and complete version of the NCCN Guidelines®, go online to NCCN.org.
ERLEADA® and mCSPC (TITAN Study)
- TITAN enrolled 1052 patients with metastatic castration-sensitive prostate cancer (mCSPC)1
- Patients in TITAN had newly diagnosed mCSPC or relapsed metastatic disease after an initial diagnosis of localized disease3
- At baseline, 63% of patients had high-volume disease and 37% of patients had low-volume disease1
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
The dual primary endpoints were overall survival and radiographic progression-free survival (rPFS).3
- ERLEADA® + ADT reduced the risk of death by 35% vs placebo + ADT (median OS: NR vs 52.2 months; HR=0.65; 95% CI: 0.53, 0.79; P<0.0001)§4
- ERLEADA® + ADT reduced the risk of radiographic progression or death by 52% vs placebo + ADT (median rPFS not estimable vs 22.1 months; HR=0.48; 95% CI: 0.39, 0.60; P<0.0001)1
§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
Consistent improvement in overall survival was observed with ERLEADA® + ADT vs placebo + ADT across the following patient subgroups1:
- Disease volume (high vs low)
- Gleason score at diagnosis (≤7 vs >7)
Consistent improvement in rPFS was observed with ERLEADA® + ADT vs placebo + ADT across the following patient subgroups1:
- Disease volume (high vs low)
- Prior docetaxel use (yes or no)
- Gleason score at diagnosis (≤7 vs >7)
ERLEADA® and nmCRPC (SPARTAN Study)
- SPARTAN enrolled 1207 patients with non-metastatic castration-resistant prostate cancer (nmCRPC)1
- Patients had a PSA doubling time ≤10 months and serum testosterone levels <50 ng/dL1,5
Conventional imaging (technetium-99m bone scans and CT scans) was used to confirm that patients were non-metastatic at screening for inclusion.5
- Yes. Patients with pelvic lymph nodes <2 cm in short axis (N1) located below the iliac bifurcation at screening were allowed in the study5
- At baseline, 16% of patients in the SPARTAN study had local or regional nodal disease (N1)5
- The primary endpoint was metastasis-free survival (MFS)5
- Metastasis-free survival (MFS) 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 first1
- Median metastasis-free survival (MFS) was 40.5 months (3.4 years) with ERLEADA® + ADT compared with 16.2 months (1.4 years) with placebo + ADT1
- ERLEADA® + ADT improved median metastasis-free survival (MFS) by 2 years (24.3 months) vs placebo + ADT (40.5 months vs 16.2 months; HR=0.28; 95% CI: 0.23, 0.35; P<0.0001)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)
In the final analysis of the SPARTAN study, ERLEADA® + ADT improved median overall survival by 14 months vs placebo + ADT (73.9 months [6.2 years] vs 59.9 months [5 years]; HR=0.78; 95% CI: 0.64, 0.96; P=0.0161).1
ADT = androgen deprivation therapy; CI = confidence interval; CRPC = castration-resistant prostate cancer; CT = computed tomography; GnRH = gonadotropin-releasing hormone; HR = hazard ratio; LHRH = luteinizing hormone-releasing hormone; mCSPC = metastatic castration-sensitive prostate cancer; NE = not estimable; nmCRPC = non-metastatic castration-resistant prostate cancer; NR = not reached; OS = overall survival; PSA = prostate-specific antigen; PSADT = prostate-specific antigen doubling time; rPFS = radiographic progression-free survival; SPARTAN = Selective Prostate Androgen Receptor Targeting with ARN-509; TITAN = Targeted Investigational Treatment Analysis of Novel Antiandrogen.
1. ERLEADA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.2.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed March 3, 2021. To view the most recent and complete version of the NCCN Guidelines®, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way.
3. 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.
4. 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. J Clin Oncol. 39(2):2294-2303.
5. 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.