Why is Real-World Evidence Important to Your Practice?

Sponsored by Johnson & Johnson

Erin Pierce, MSN, APRN, AOCNP, is an experienced advanced oncology nurse practitioner specializing in genitourinary cancers. She currently serves as a key member of the clinical team at HonorHealth Research Institute in Arizona, where she plays an active role in advancing treatment strategies for patients with prostate cancer and other urologic malignancies. Throughout her oncology nursing experience, Erin has developed a strong focus on clinical research and the integration of real-world evidence into care decisions. She collaborates closely with multidisciplinary teams to support evidence-based treatment planning and has worked with leading clinical trials aimed at improving outcomes for patients with advanced prostate cancer. Erin is board certified as an Advanced Oncology Certified Nurse Practitioner (AOCNP) and holds a Master of Science in Nursing. Erin has been compensated by Johnson & Johnson to share her perspective.

Written by Erin Pierce, MSN, APRN, AOCNP

A few years ago, I had a patient who affectionately went by the name “Pops.” At 85 years young, he was full of life and juggling multiple health issues alongside prostate cancer, yet determined not to let cancer stop him. He’s the kind of patient we see in our clinic all the time but rarely the kind reflected in clinical trial data.

This is where real-world evidence (RWE) becomes essential, and where advanced practice providers (APPs) can play a critical role. As APPs, we are often the ones guiding patients like “Pops” through complex medical decisions, from treatment planning to survivorship. While randomized clinical trials (RCTs) are foundational, they may not always capture the diverse circumstances we see in everyday clinical practice.¹

RWE helps bridge that gap with data drawn from real-world settings—offering the insights to help address the unique needs of patients like “Pops” in ways traditional trials may not.²

Filling Gaps in Clinical Trials

As APPs, we often care for patients with complex medical situations who aren’t the typical clinical trial patients. These patients may present with multiple comorbidities. It is these very nuances that make real-world evidence essential in providing everyday care.

During the first nine years of my practice in New Orleans, Louisiana, about 60% of the prostate cancer patients I treated were men of underrepresented groups who also have a higher risk of developing prostate cancer such as African American and Caribbean men of African ancestry.³ That’s where RWE plays such a pivotal role in my conversations with these patients, helping us fill those gaps and make treatment decisions that are truly patient centered.

Connecting Data to Daily Practice

As APPs, we manage care of patients, track disease progression, support survivorship, and help patients overcome barriers to care. We do it all, but to do it well we need data that reflects the complexity of our real-world patients.

Randomized controlled trials are considered the gold standard for determining treatment efficacy.¹ RWE offers complementary insights into how treatments perform in everyday clinical practice outside of trial settings.⁴ That evidence, coupled with RCTs, can help inform patient-centered care decisions.⁵

These insights are particularly relevant when evaluating treatment options like ERLEADA^®(apalutamide), which has been studied in both randomized clinical trials and real-world settings.

The efficacy of ERLEADA^® was evaluated in a phase 3, multicenter, double-blind, placebo-controlled trial in metastatic castration-sensitive prostate cancer (mCSPC) patients (N=1052) randomized (1:1) to receive either ERLEADA^® 240 mg once daily (N=525) or placebo once daily (N=527). All patients in the trial received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a prior bilateral orchiectomy. The dual primary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS).⁶

ERLEADA^® + androgen deprivation therapy (ADT) demonstrated a 35% reduction in the risk of death compared with ADT alone in the final OS analysis (hazard ratio [HR]=0.65, confidence interval [CI]: 0.53, 0.79; Median OS: not reached [NR] vs 52.2 months; median follow-up time: 44.0 months) and a 52% reduction in the risk of radiographic progression or death (HR=0.48, CI: 0.39, 0.60; Median rPFS: not estimable [NE] vs 22.1 months; median follow-up time was 22.7 months).⁶

The most common adverse reactions (≥10%) that occurred more frequently in the ERLEADA^®-treated patients (≥2% over placebo) were rash, hot flash, hypertension, arthralgia, and pruritus.⁶

In prostate cancer, recent data underscores the importance of early, informed treatment. A real-world study of nearly 4,000 patients with mCSPC showed a ~23% lower risk of death 2 years after initiating treatment for those who were newly started on an androgen receptor pathway inhibitor (ARPI) treatment, in this case ERLEADA^®, compared with enzalutamide.^6,7

In that analysis (ERLEADA^® n=1,810; enzalutamide n=1,909), the adjusted hazard ratio at 24 months was 0.77 (95% CI 0.62-0.96; P=0.019).⁸

This study had⁷:

• Pre-Specified Protocol: This provides transparency and allows for replication of the study
• Pre-Specified Primary Endpoint: OS at 24 months. Data required to be reported even if inferior finding
• Power Calculation: This provides an understanding of how many patients are required in both arms of the trial to determine a meaningful difference between the cohorts/treatment groups
• Propensity Score Weighting (Inverse Probability of Treatment Weighting [IPTW]): This methodology was employed to adjust for baseline differences in patient characteristics replicating the conditions of a randomized clinical trial (RCT)

This study was not designed to assess differences in safety between cohorts.

The limitations for this study included⁷:

• Potential for miscoded, misclassified, or missing data in clinical record
• Regression analyses could only adjust for documented covariate
• Unlike Phase 3 trials assessing OS at specific events, this study evaluated survival at 24 months
• Longer follow-up studies may be needed to fully assess the therapeutic effects

When you have several options within the same clinical space, it is often hard for one to determine which is the best option. This is when real-world outcomes can really shine and give us powerful tools to guide our patients through some of their most critical early treatment decisions and adherence. Patient adherence is a critical factor influencing overall survival in real-world settings.

Flexible dosing options for ERLEADA^® including alternate administration methods for those who have difficulty swallowing tablets—once daily, no food requirements, and 100% absorption—are designed to accommodate patient preferences and needs, supporting both start and continuation of therapy.⁸

Turning Data Into Dialogue

As clinicians trained with a holistic, patient-centered lens, APPs are natural educators and advocates, helping patients feel confident and informed about their treatment decisions. But building trustful relationships and helping patients navigate this data takes time. That starts with understanding each individual patient and meeting them where they are. So, when I say, “This is what I think is best for you,” I get their attention—because they know that my decision comes from a caring and empathetic heart, not just a protocol.

Patients today want to know what to expect, not just in trials but in real life.

Putting Real-World Evidence to Work

In today’s prostate cancer landscape, APPs serve a vital role in the care team—we’re evidence translators, trust builders, and often the first to guide patients through complex treatment choices. We spend the time explaining the risks in everyday language to help patients confidently move forward. RWE coupled with RCTs makes those conversations more powerful because it reflects the diverse circumstances our patients face.⁵

Our perspective matters, and RWE and RCTs give us the credibility and clarity to speak up about what we see in our clinics. It’s time we use that voice even more.

To better serve our diverse patients, we need to engage with all the data available, ask how it fits the needs of our patient populations, and apply it in practice. It’s not just about what the data say—it’s about how it helps you provide comprehensive prostate care. Patients like “Pops” may not qualify for a clinical trial, but they still deserve evidence-based, compassionate care. RWE and RCTs equip us to meet them where they are and guide them where they need to go.

By staying engaged with emerging evidence, we can help ensure every treatment decision we make is rooted in both science and compassion.

References

1. Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med. 2000; 342:1887–1892.
   doi: 10.1056/NEJM20000622342250 
2. Sherman RE, Anderson SA, Dal Pan GJ, et al. Real-world evidence — what is it and what can it tell ss? N Engl J Med. 2016;375:2293–2297. doi: 10.1056/NEJMsb1609216
3. American Cancer Society. Key statistics for prostate cancer. Accessed June 2025. https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
4. Blonde L, Khunti K, Harris SB, et al. Interpretation and impact of real-world clinical data for the practicing clinician. Adv Ther. 2018;35(11):1763-1774. doi: 10.1007/s12325-018-0805-y
5. Costa V, Custodio MG, Gefen E, et al. The relevance of the real-world evidence in research, clinical, and regulatory decision making. Front Public Health. 2025;13:1512429. https://doi.org/10.3389/fpubh.2025.1512429
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.
   J Clin Oncol. 2021;39(20):2294-2303. doi: 10.1200/JCO.20.03488
7. Bilen MA, Lowentritt B, Khilfeh I, et al. Overall survival with apalutamide versus enzalutamide in metastatic castration-sensitive prostate cancer. Adv Ther. 2025 May 29. doi: 10.1007/s12325-025-03207-6. Epub ahead of print. PMID: 40439959.
8. ERLEADA^® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.

© Johnson & Johnson and its affiliates 2025 12/25 cp-524690v1

INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR ERLEADA^®

INDICATIONS

ERLEADA^® (apalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with:

• Metastatic castration-sensitive prostate cancer (mCSPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

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 full Prescribing Information for ERLEADA^®.

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