BARCELONA, Spain--(BUSINESS WIRE)--The Janssen Pharmaceutical Companies of Johnson & Johnson today announced updated, longer-term results from the pivotal Phase 3 SPARTAN study following a second interim analysis. Treatment with ERLEADA® (apalutamide) plus androgen deprivation therapy (ADT) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were at high-risk of developing metastases, resulted in a 25 percent reduction in the risk of death compared with placebo plus ADT [HR=0.75; 95 percent CI, 0.59–0.96; p=0.0197 (to reach statistical significance, a p-value of p<0.0121 needed to be observed)].1,2
The updated findings showed overall survival (OS) results supported the first interim analysis, despite a crossover of placebo patients to the apalutamide treatment group.1,2 Results were presented in an oral session at the 2019 European Society for Medical Oncology (ESMO) Annual Congress (abstract #843O), and simultaneously published in Annals of Oncology.
At the second interim analysis, a longer median follow-up of 41 months, four-year OS rates were 72.1 percent for patients treated with apalutamide and 64.7 percent for patients treated with placebo.1,2 The OS benefit of apalutamide was consistent across baseline subgroups, such as race, prior treatments, baseline PSA and performance status.1,2
This interim analysis took place when 67 percent of the required OS events had been observed, compared with the original report when only 24 percent of required OS events had occurred (HR=0.70; 95 percent CI, 0.47–1.04; p=0.07).1,2 After unblinding the study, and prior to the second interim analysis, 76 non-progressing patients in the placebo group (19 percent of all placebo patients) crossed over to open-label apalutamide for an average of 15 months; the OS rates in the placebo group included those patients who were crossed over to apalutamide treatment, thereby underestimating the true treatment effect.1,2 The rates of treatment-emergent adverse events for apalutamide at the second interim analysis were consistent with rates previously reported.1,2 In the SPARTAN study, the most common adverse events (≥10 percent) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, falls, hot flush, decreased appetite, fracture and peripheral edema.3
“The data presented at ESMO 2019 add to the growing body of evidence demonstrating a trend for survival benefit achieved by apalutamide in patients with high-risk nmCRPC. This interim analysis for survival is in line with the initial data presented for all androgen signaling inhibitors in this disease setting. Hence all data presented to date reinforce the benefit of treating men with non-metastatic (by conventional imaging) castration-resistant prostate cancer,” said Dr Eleni Efstathiou, MD, PhD, Associate Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, U.S. “For nmCRPC patients who remain at risk of their cancer spreading, and the clinicians that treat them, these data are very encouraging as they show the potential of this treatment in improving survival rates and slowing progression to a fatal stage of the disease – the ultimate goal when treating this population.”
Initial results from the SPARTAN trial were presented at the 2018 American Society of Clinical Oncology Genitourinary Annual Meeting Cancers Symposium (ASCO GU), and simultaneously published in The New England Journal of Medicine.4,5
“Despite many advances in the treatment of prostate cancer in recent years, there remains a high unmet need, particularly in the treatment of those patients who are at risk of their disease progressing to the most advanced form; the metastatic disease stage,” said Dr Joaquín Casariego, Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A.. “We are very excited to share these new data from the SPARTAN trial, which reinforces the importance of apalutamide as a treatment option for patients with high-risk nmCRPC, for whom delaying the onset of metastases becomes a crucial objective in their disease journey. We will persist in our efforts to improve outcomes for patients through our robust research programme and remain committed to achieving our goal of making prostate cancer a manageable or even a curable disease.”
About the SPARTAN study
SPARTAN (NCT01946204) was a Phase 3, randomised, double-blind, placebo-controlled, multicentre study that evaluated ERLEADA® (apalutamide) in combination with ADT in patients with high-risk nmCRPC with a rapidly rising PSA (PSA Doubling Time ≤10 months).4 The SPARTAN study enrolled 1,207 patients who were randomised 2:1 to receive either apalutamide orally at a dose of 240 mg once daily in combination with ADT (n=806) or placebo once daily in combination with ADT (n=401).4 Study results were initially reported at the 2018 ASCO Genitourinary Cancers Symposium and published in The New England Journal of Medicine.4,5
In the SPARTAN study, the most common adverse reactions (≥10 percent) were fatigue, hypertension, rash, diarrhea, nausea, decreased weight, arthralgia, falls, hot flushes, decreased appetite, bone fractures and peripheral edema.1
About non-metastatic castration-resistant prostate cancer
Non-metastatic castration-resistant prostate cancer (nmCRPC) refers to a disease stage when the cancer no longer responds to treatments that lower testosterone but has not yet been discovered in other parts of the body using a total body bone scan and CT/MRI scan.6 Features include: lack of detectable metastatic disease; rapidly rising prostate-specific antigen while on ADT with serum testosterone level below 50 ng/dL.7,8 Ninety percent of patients with nmCRPC will eventually develop metastases, which can lead to pain, fractures and other symptoms.9 The relative five-year survival rate for patients diagnosed at a distant-stage prostate cancer is 30 percent.10 It is critical to delay the development of metastasis in patients with nmCRPC.
About ERLEADA® (apalutamide)
ERLEADA® (apalutamide) is an androgen receptor (AR) inhibitor indicated for use in Europe for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.3 In the U.S. apalutamide is indicated for the treatment of nmCRPC and metastatic castration-sensitive prostate cancer.11 Apalutamide is currently under review by the European Medicines Agency (EMA) for the treatment of metastatic hormone-sensitive prostate cancer.12
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.
Learn more at www.janssen.com/emea. Follow us at www.twitter.com/janssenEMEA for our latest news. Janssen-Cilag S.A., Janssen R&D, LLC and Janssen Biotech are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
1 Smith, M, et al. Apalutamide and Overall Survival in Patients with Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): Updated Results from the Phase 3 SPARTAN Study. Annals of Oncology (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248. Accessed September 2019.
2 Smith, M, et al. Apalutamide and Overall Survival in Patients with Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): Updated Results from the Phase 3 SPARTAN Study. 2019 European Society for Medical Oncology. Abstract #843O.
3 European Medicines Agency. Erleada. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/erleada#authorisation-details-section. Accessed September 2019.
4 Smith, M, et al. Apalutamide Treatment and Metastasis-Free Survival in Prostate Cancer. N Engl J Med. 2018; 378:1408–1418. Accessed September 2019.
5 Small E., et al. SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) vs placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). 2018 Genitourinary Cancers Symposium. Abstract #161.
6 Scher HI, et al. 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;26:1148–1159. Accessed September 2019.
7 Scher HI, et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34:1402–1418. Accessed September 2019.
8 Virgo K, et al. Second-Line Hormonal Therapy for Men with Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion. J Clin Oncol. 2017; 0732-183X/17/3599-1. Accessed September 2019.
9 Saad F, et al. The 2015 CUA0CUOG guidelines for the management of castration-resistant prostate cancer (CRPC). Can Urol Assoc J. 2015;9(3–4):90–96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455631/. Accessed September 2019.
10 American Cancer Society. Cancer Facts & Figures. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf. Accessed September 2019.
11 ERLEADA product information Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210951s000lbl.pdf. Accessed September 2019.
12 Janssen. Janssen Seeks to Expand Use of ERLEADA® (apalutamide) in the Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/final_approved_erleada_ema_filing_press_release_20190604.pdf Accessed September 2019.