Study highlights opportunity for treatment intensification in
this population since approximately 50% of patients with high-risk
localized prostate cancer (HRLPC) experience disease recurrence
within two years of surgery
SAN
ANTONIO, May 3, 2024 /PRNewswire/ -- Johnson
& Johnson announced today results from the open-label,
single-arm Phase 2 Apa-RP study evaluating adjuvant treatment with
ERLEADA® (apalutamide) and androgen deprivation therapy
(ADT) in patients with HRLPC who have undergone radical
prostatectomy (RP). Following RP, patients who received the
treatment regimen showed a 100% biochemical recurrence (BCR)–free
rate at 24 months.1 These data were presented today at
an Oral Presentation Session (Abstract #P2-07) at the 2024 American
Urological Association Annual Meeting AUA, May 3-6, 2024, in San
Antonio, Texas.
"Findings from the Apa-RP study support the benefit of treatment
intensification with apalutamide and androgen deprivation therapy
following radical prostatectomy for patients who are at high risk
for BCR and thus progression to metastatic prostate cancer," said
Neal Shore, M.D., F.A.C.S., Steering
Committee Chair and Chief Medical Officer, Surgical Oncology and
Urology, Genesis Care.* "Results
from this study encourage additional research for high-risk
localized prostate cancer and highlight the promise of bringing
treatment into earlier stages of disease following radical
prostatectomy."
The study met its primary endpoint, showing that patients who
received 12 months of ERLEADA® plus ADT adjuvant to RP
experienced no confirmed biochemical recurrence after 12 additional
months of follow-up. The treatment regimen demonstrated a serum
testosterone recovery (≥150 ng/dL) rate of 76.4% at 12 months (95%
CI, 65.0–84.5). The safety profile of ERLEADA® with ADT
was consistent with previous reports: treatment-emergent adverse
events (TEAEs) were reported by 99.1% of patients; 22.2% of TEAEs
were grade 3-4.1
"Despite treatment advancements over the last decade, half of
patients with high-risk localized prostate cancer experience
disease recurrence less than two years after radical prostatectomy,
highlighting a need for treatment options that reduce longer-term
risks," said Luca Dezzani, M.D.,
Vice President, Medical Affairs, Solid Tumor, Johnson & Johnson
Innovative Medicine. "Studies like Apa-RP coupled with the
continued evaluation of ERLEADA® in ongoing Phase 3
studies are critical steps in understanding the full potential of
earlier treatment intervention, with the ultimate goal of improving
patient outcomes."
Approximately 300,000 people are diagnosed with prostate cancer
each year in the U.S.2 Up to 40% of patients will be
classified as high-risk.3 Despite advancements in
treatment, disease recurrence remains substantial; up to 50% of
patients within ten years of surgery experience recurrence and
carry a significant risk of disease progression and
death.4
About Apa-RP
The Phase 2 multicenter, open-label
single-arm study (NCT04523207) evaluated 108 patients across 32
U.S. community urologic practices. Patients were treatment-naïve
with HRLPC who had undergone RP and were treated with
ERLEADA® (240 mg, once daily) for 12 cycles (1 cycle =
28 days) and ADT for 12 months. The primary endpoint evaluated
BCR-free rate, defined as two sequential prostate-specific antigen
(PSA) levels of <=0.2 ng/mL. The secondary endpoints included
testosterone recovery rate and safety.
About ERLEADA®
ERLEADA® (apalutamide) is an androgen receptor
inhibitor indicated for the treatment of patients with
non-metastatic castration-resistant prostate cancer (nmCRPC) and
for the treatment of patients with metastatic castration-sensitive
prostate cancer (mCSPC).
ERLEADA® received U.S. Food and Administration
(FDA) approval for nmCRPC in February 2018
and received U.S. FDA approval for mCSPC in September
2019. To date, more than 200,000 patients worldwide have been
treated with ERLEADA®. Additional studies are ongoing in
the evaluation of ERLEADA® for the treatment of
localized high-risk or locally advanced prostate cancer including
the Phase 3 ATLAS 15 (NCT02531516) and PROTEUS (NCT03767244)
studies.
For more information, visit www.ERLEADA.com.
ERLEADA® IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Cerebrovascular and Ischemic Cardiovascular Events —
In a randomized study (SPARTAN) of patients with nmCRPC, ischemic
cardiovascular events occurred in 3.7% of patients treated with
ERLEADA® and 2% of patients treated with placebo.
In a randomized study (TITAN) in patients with mCSPC, ischemic
cardiovascular events occurred in 4.4% of patients treated with
ERLEADA® and 1.5% of patients treated with placebo.
Across the SPARTAN and TITAN studies, 4 patients (0.3%) treated
with ERLEADA® and 2 patients (0.2%) treated with
placebo died from an ischemic cardiovascular event. Patients with
history of unstable angina, myocardial infarction, congestive heart
failure, stroke, or transient ischemic attack within 6 months of
randomization were excluded from the SPARTAN and TITAN studies.
In the SPARTAN study, cerebrovascular events occurred in 2.5% of
patients treated with ERLEADA® and 1% of patients
treated with placebo. In the TITAN study, cerebrovascular events
occurred in 1.9% of patients treated with
ERLEADA® and 2.1% of patients treated with placebo.
Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated
with ERLEADA®, and 2 patients (0.2%) treated with
placebo died from a cerebrovascular event.
Cerebrovascular and ischemic cardiovascular events, including
events leading to death, occurred in patients receiving
ERLEADA®. Monitor for signs and symptoms of ischemic
heart disease and cerebrovascular disorders. Optimize management of
cardiovascular risk factors, such as hypertension, diabetes, or
dyslipidemia. Consider discontinuation of
ERLEADA® for Grade 3 and 4 events.
Fractures — In a randomized study (SPARTAN) of
patients with nmCRPC, fractures occurred in 12% of patients treated
with ERLEADA® and in 7% of patients treated with
placebo. In a randomized study (TITAN) of patients with mCSPC,
fractures occurred in 9% of patients treated with
ERLEADA® and in 6% of patients treated with
placebo. Evaluate patients for fracture risk. Monitor and manage
patients at risk for fractures according to established treatment
guidelines and consider use of bone-targeted agents.
Falls — In a randomized study (SPARTAN), falls
occurred in 16% of patients treated with
ERLEADA® compared with 9% of patients treated with
placebo. Falls were not associated with loss of consciousness or
seizure. Falls occurred in patients receiving
ERLEADA® with increased frequency in the elderly.
Evaluate patients for fall risk.
Seizure — In two randomized studies (SPARTAN and
TITAN), 5 patients (0.4%) treated with ERLEADA® and
1 patient treated with placebo (0.1%) experienced a seizure.
Permanently discontinue ERLEADA® in patients who
develop a seizure during treatment. It is unknown whether
anti-epileptic medications will prevent seizures with
ERLEADA®. Advise patients of the risk of developing a
seizure while receiving ERLEADA® and of engaging in
any activity where sudden loss of consciousness could cause harm to
themselves or others.
Severe Cutaneous Adverse Reactions — Fatal and
life-threatening cases of severe cutaneous adverse reactions
(SCARs), including Stevens-Johnson syndrome/toxic epidermal
necrolysis (SJS/TEN), and drug reaction with eosinophilia and
systemic symptoms (DRESS) occurred in patients receiving
ERLEADA®.
Monitor patients for the development of SCARs. Advise patients
of the signs and symptoms of SCARs (eg, a prodrome of fever,
flu-like symptoms, mucosal lesions, progressive skin rash, or
lymphadenopathy). If a SCAR is suspected, interrupt
ERLEADA® until the etiology of the reaction has
been determined. Consultation with a dermatologist is recommended.
If a SCAR is confirmed, or for other Grade 4 skin reactions,
permanently discontinue ERLEADA® [see Dosage and
Administration (2.2)].
Embryo-Fetal Toxicity — The safety and efficacy of
ERLEADA® have not been established in females.
Based on findings from animals and its mechanism of action,
ERLEADA® can cause fetal harm and loss of pregnancy
when administered to a pregnant female. Advise males with female
partners of reproductive potential to use effective contraception
during treatment and for 3 months after the last dose of
ERLEADA® [see Use in Specific Populations (8.1,
8.3)].
ADVERSE REACTIONS
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.
Laboratory Abnormalities — All Grades (Grade 3-4)
- Hematology — In the TITAN study: white blood cell
decreased ERLEADA® 27% (0.4%), placebo 19% (0.6%). In
the SPARTAN study: anemia ERLEADA® 70% (0.4%),
placebo 64% (0.5%); leukopenia ERLEADA® 47% (0.3%),
placebo 29% (0%); lymphopenia ERLEADA® 41% (1.8%),
placebo 21% (1.6%)
- Chemistry — In the TITAN study: hypertriglyceridemia
ERLEADA® 17% (2.5%), placebo 12% (2.3%). In the
SPARTAN study: hypercholesterolemia ERLEADA® 76%
(0.1%), placebo 46% (0%); hyperglycemia
ERLEADA® 70% (2%), placebo 59% (1.0%);
hypertriglyceridemia ERLEADA® 67% (1.6%), placebo
49% (0.8%); hyperkalemia ERLEADA® 32% (1.9%),
placebo 22% (0.5%)
Rash — In 2 randomized studies (SPARTAN and TITAN),
rash was most commonly described as macular or maculopapular.
Adverse reactions of rash were 26% with ERLEADA® vs
8% with placebo. Grade 3 rashes (defined as covering >30% body
surface area [BSA]) were reported with
ERLEADA® treatment (6%) vs placebo (0.5%).
The onset of rash occurred at a median of 83 days. Rash resolved
in 78% of patients within a median of 78 days from onset of rash.
Rash was commonly managed with oral antihistamines, topical
corticosteroids, and 19% of patients received systemic
corticosteroids. Dose reduction or dose interruption occurred in
14% and 28% of patients, respectively. Of the patients who had dose
interruption, 59% experienced recurrence of rash upon
reintroduction of ERLEADA®.
Hypothyroidism — In 2 randomized studies (SPARTAN
and TITAN), hypothyroidism was reported for 8% of patients treated
with ERLEADA® and 1.5% of patients treated with
placebo based on assessments of thyroid-stimulating hormone (TSH)
every 4 months. Elevated TSH occurred in 25% of patients treated
with ERLEADA® and 7% of patients treated with
placebo. The median onset was at the first scheduled assessment.
There were no Grade 3 or 4 adverse reactions. Thyroid replacement
therapy, when clinically indicated, should be initiated or dose
adjusted.
DRUG INTERACTIONS
Effect of Other Drugs on ERLEADA® —
Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is
predicted to increase the steady-state exposure of the active
moieties. No initial dose adjustment is necessary; however, reduce
the ERLEADA® dose based on tolerability [see
Dosage and Administration (2.2)].
Effect of ERLEADA® on Other Drugs
CYP3A4, CYP2C9, CYP2C19, and UGT Substrates —
ERLEADA® is a strong inducer of CYP3A4 and CYP2C19,
and a weak inducer of CYP2C9 in humans. Concomitant use of
ERLEADA® with medications that are primarily
metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower
exposure to these medications. Substitution for these medications
is recommended when possible or evaluate for loss of activity if
medication is continued. Concomitant administration of
ERLEADA® with medications that are substrates of
UDP-glucuronosyl transferase (UGT) can result in decreased
exposure. Use caution if substrates of UGT must be co-administered
with ERLEADA® and evaluate for loss of
activity.
P-gp, BCRP, or OATP1B1 Substrates — Apalutamide is a weak
inducer of P-glycoprotein (P-gp), breast cancer resistance protein
(BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1)
clinically. Concomitant use of ERLEADA® with
medications that are substrates of P-gp, BCRP, or OATP1B1 can
result in lower exposure of these medications. Use caution if
substrates of P-gp, BCRP, or OATP1B1 must be co-administered with
ERLEADA® and evaluate for loss of activity if
medication is continued.
Please see the full Prescribing
Information for ERLEADA®.
About Johnson & Johnson
At Johnson &
Johnson, we believe health is everything. Our strength in
healthcare innovation empowers us to build a world where complex
diseases are prevented, treated, and cured, where treatments are
smarter and less invasive, and solutions are personal. Through our
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positioned to innovate across the full spectrum of healthcare
solutions today to deliver the breakthroughs of tomorrow and
profoundly impact health for humanity. Learn more at
https://www.jnj.com/ or at
www.janssen.com/johnson-johnson-innovative-medicine. Follow us
at @JanssenUS and @JNJInnovMed. Janssen Research &
Development, LLC, and Janssen Biotech, Inc., are both Johnson &
Johnson companies.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995
regarding product development and the potential benefits and
treatment impact of ERLEADA® (apalutamide). The reader
is cautioned not to rely on these forward-looking statements. These
statements are based on current expectations of future events. If
underlying assumptions prove inaccurate or known or unknown risks
or uncertainties materialize, actual results could vary materially
from the expectations and projections of Janssen Research &
Development, LLC, Janssen Biotech, Inc., and/or Johnson &
Johnson. Risks and uncertainties include, but are not limited to:
challenges and uncertainties inherent in product research and
development, including the uncertainty of clinical success and of
obtaining regulatory approvals; uncertainty of commercial success;
manufacturing difficulties and delays; competition, including
technological advances, new products and patents attained by
competitors; challenges to patents; product efficacy or safety
concerns resulting in product recalls or regulatory action; changes
in behavior and spending patterns of purchasers of health care
products and services; changes to applicable laws and regulations,
including global health care reforms; and trends toward health care
cost containment. A further list and descriptions of these risks,
uncertainties and other factors can be found in Johnson &
Johnson's Annual Report on Form 10-K for the fiscal year ended
December 31, 2023, including in the
sections captioned "Cautionary Note Regarding Forward-Looking
Statements" and "Item 1A. Risk Factors," and in Johnson &
Johnson's subsequent Quarterly Reports on Form 10-Q and other
filings with the Securities and Exchange Commission. Copies of
these filings are available online at www.sec.gov, www.jnj.com or
on request from Johnson & Johnson. None of Janssen Research
& Development, LLC, Janssen Biotech, Inc., nor Johnson &
Johnson undertakes to update any forward-looking statement as a
result of new information or future events or developments.
*Dr. Shore has not been paid for any media work.
1 Shore N, Hafron J, Saltzstein D, Brown G, Belkoff
L, Aggarawal P, et al. P2-07 apalutamide for high-risk localized
prostate cancer following radical prostatectomy in Apa-RP: a
multicenter, open-label, single-arm phase 2 study. Journal of
Urology. 2024:211.
2 Key statistics for prostate cancer. American Cancer
Society. Accessed April 2, 2024.
https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
3 Cooperberg MR, Cowan J, Broering JM, Carroll PR.
High-risk prostate cancer in the United
States, 1990-2007. World J Urol. 2008;26(3):211-218.
doi: 10.1007/s00345-008-0250-7. Epub 2008 Mar 28. PMID: 18369637;
PMCID: PMC2948572
4 Napodano G, Ferro M, Sanseverino R. High-risk prostate
cancer: A very challenging disease in the field of uro-oncology.
Diagnostics (Basel).
202126;11(3):400. doi: 10.3390/diagnostics11030400. PMID: 33652852;
PMCID: PMC7996958
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