Largest head-to-head real-world study in mCSPC
demonstrated that ERLEADA® reduced risk of death by 23
percent at 24 months compared to enzalutamide
LISBON,
Portugal, Oct. 2, 2024 /PRNewswire/ -- Johnson
& Johnson (NYSE: JNJ) today announced the results of a landmark
real-world, head-to-head study showing that ERLEADA®
(apalutamide) provided a statistically significant overall survival
benefit at 24 months compared to enzalutamide in patients with
metastatic castration-sensitive prostate cancer (mCSPC). Presented
at the 6th European Congress of Oncology Pharmacy (ECOP) in
Lisbon, Portugal, on October 2 (Abstract #P31), this study of nearly
4,000 patients represents the largest real-world, head-to-head
analysis of these two androgen receptor pathway inhibitors (ARPIs)
in mCSPC.
The study applied U.S. Food and Drug Administration (FDA)
real-world evidence guidance and employed robust methodology, data
sources and a large, diverse cohort to ensure validity of its
findings. The retrospective study identified mCSPC patients who
initiated ERLEADA® or enzalutamide between December 16, 2018 – December 31, 2023, based on patient data in
electronic databases. There were 1,800 ERLEADA® and
1,909 enzalutamide initiators who met study criteria.
The analysis demonstrated patients with mCSPC who initiated
ERLEADA® as their first ARPI had a statistically
significant 23 percent reduction in their risk of death at 24
months compared to patients who initiated on enzalutamide (hazard
ratio [HR], 0.77; 95% confidence interval [CI],
0.62-0.96; P<0.019). The proportion of patients
alive at 24 months (87.6 percent) observed in the
ERLEADA® cohort in this real-world analysis is
consistent with that in the Phase 3 TITAN trial (82.4
percent).1 TITAN demonstrated a statistically
significant superior overall survival benefit of
ERLEADA® plus androgen deprivation therapy (ADT)
compared to ADT alone at the primary analysis after a median 22.7
months of follow-up (HR 0.67; 95% CI,
0.51-0.89; P=0.005) and at the final analysis after a
median 44 months of follow-up (HR 0.65; 95% CI,
0.53-0.79; P<0.0001).1,2
"This real-world evidence showed a statistically significant and
clinically meaningful improvement in survival with apalutamide over
enzalutamide in patients with mCSPC at 24 months," said
Neal Shore, M.D., F.A.C.S., Steering
Committee Chair and Medical Director, Carolina Urologic Research
Center and study investigator.* "Head-to-head, randomized and
controlled Phase 3 studies have been the gold standard for
comparing the effectiveness of oncology medicines, however,
prospective ARPI comparator trials have not been conducted. This
real-world study is provocative as the comprehensive data and
rigorous methodology used in this study offers real-world insights
on overall survival which can provide prescribers with information
to consider when choosing an ARPI."
"ERLEADA is the only ARPI to demonstrate a survival benefit as
early as 22 months, as seen in the TITAN study. Since ERLEADA's
approval, multiple ARPIs have been introduced, but no one has
directly compared their effectiveness on a large scale – until
now," said Luca Dezzani, M.D., U.S.
Vice President, Medical Affairs, Solid Tumors, Johnson &
Johnson Innovative Medicine. "With a decade-plus legacy in prostate
cancer, we have pushed the field further with this additional
evidence showing an overall survival benefit with ERLEADA, which is
a patient-centric option taken as just one pill, once daily."
Some limitations of this study include potential miscoding or
missing information in the data sources; however, the data sources
used in this study were deemed fit for purpose to identify the
patient population correctly and to assess survival. Lastly, while
survival was assessed at 24 months for statistical comparison,
longer-term studies are needed to fully evaluate the therapeutic
effects of these treatments.
About Prostate Cancer
Approximately 300,000
people are diagnosed with prostate cancer each year in the
U.S.3 Up to 40 percent of patients will be classified as
high-risk.4 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.5 It's estimated that
more than 35,000 men will succumb to their prostate cancer in 2024,
which reinforces the importance of choosing the best possible
therapy early for patients with advanced prostate
cancer.3
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. ERLEADA® is the first and only
next-generation androgen receptor inhibitor offering a
once-daily, single-tablet treatment option for patients. 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 (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)].
Interstitial Lung Disease (ILD)/Pneumonitis — Fatal and
life-threatening interstitial lung disease (ILD) or pneumonitis can
occur in patients treated with ERLEADA®.
Post-marketing cases of ILD/pneumonitis, including fatal cases,
occurred in patients treated with ERLEADA®. Across
clinical trials (TITAN and SPARTAN, n=1327), 0.8% of patients
treated with ERLEADA® experienced ILD/pneumonitis,
including 0.2% who experienced Grade 3 events [see Adverse
Reactions (6.1, 6.2)].
Monitor patients for new or worsening symptoms indicative of
ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold
ERLEADA® if ILD/pneumonitis is suspected. Permanently
discontinue ERLEADA® in patients with severe
ILD/pneumonitis or if no other potential causes of ILD/pneumonitis
are identified [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 expertise in
Innovative Medicine and MedTech, we are uniquely 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 www.jnj.com or at
www.innovativemedicine.jnj.com. Follow us
at @JanssenUS and @JNJInnovMed. Janssen Research &
Development, LLC, and Janssen Biotech, Inc. are 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 provided consulting, advisory, and speaking
services to Janssen; he has not been paid for any media
work.
1 Chi KN, Agarwal, N, Bjartell, A, et al. Apalutamide
for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J
Med. 2019;381(1):13-24. doi: 10.1056/NEJMoa1903307
2 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. 2021;39(20):2294-2303. doi:
10.1200/JCO.20.03488
3 Key statistics for prostate cancer. American Cancer
Society. Accessed September 2024.
https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
4 Cooperberg MR, Cowan J, Broering JM, et al. 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.
5 Napodano G, Ferro M, Sanseverino R. High-risk prostate
cancer: A very challenging disease in the field of uro-oncology.
Diagnostics (Basel).
2021;11(3):400. doi: 10.3390/diagnostics11030400.
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