A Study to Test if Enzalutamide is Effective and Safe in Prostate Cancer Patients Who Have Never Had Hormone Therapy

A Study to Test if Enzalutamide is Effective and Safe in Prostate Cancer Patients Who Have Never Had Hormone Therapy

A Phase 2, Open-label, Single-arm, Efficacy and Safety Study of Enzalutamide (MDV3100) in Patients With Hormone-naïve Prostate Cancer

To evaluate the effect of enzalutamide on prostate specific antigen (PSA) level in men with prostate cancer.

Participants received oral enzalutamide at 160 mg once daily for 24 weeks. Participants who had clinical benefit at Week 25 could continue to receive enzalutamide until disease progression, objective or clinical, or occurrence of an unacceptable toxicity, at the discretion of the investigator.

A PSA response was defined as a decline from Baseline in PSA level of 80% or greater. Blood samples for PSA were collected and analyzed at a central laboratory. Participants with an unknown or missing response or who discontinued prior to week 25 for any reason were treated as non-responders.

Each adverse event (AE) was assessed by the investigator for causal relationship to the study drug; those deemed possibly or probably related to study drug are reported as drug regimen related AEs (DRRAEs). A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Resulted in death Was life-threatening Resulted in persistent or significant disability/incapacity Resulted in congenital anomaly or birth defect Required inpatient hospitalization or led to prolongation of hospitalization Other medically important events.

From first dose of study drug up to 30 days after last dose of study drug; median duration of treatment of 1666.0 days (range of 52-2052)

A PSA response was defined as a decline from baseline in PSA level of 80% or greater. Blood samples for PSA were collected and analyzed at a central laboratory. Participants with an unknown or missing response or who discontinued prior to week 49, week 97 or week 169 for any reason were treated as non-responders.

Participants with unknown or missing PSA results at week 25 or who discontinued prior to week 25 were considered non-responders at week 25. Participants with unknown or missing PSA results at week 49, week 97 or week 169 were considered non-responders.

Participants with unknown or missing PSA results at week 25 or who discontinued prior to Week 25 were considered non-responders at Week 25. Participants with unknown or missing PSA results at week 49, 97 and 169 were considered non-responders.

Participants with unknown or missing PSA results at week 25 or who discontinued prior to week 25 were considered non-responders at week 25. Participants with unknown or missing PSA results at week 49, 97 or 169 were considered non-responders.

The maximum decline from Baseline in PSA was calculated as the largest reduction from Baseline in PSA level that occurred at any point after treatment start up to week 25 and up to and including the assessment made at the safety follow-up visit, divided by the PSA Baseline value and multiplied by 100, i.e., the maximum percent change from baseline.

Baseline to Week 25 and from Baseline up to the EOS date of 27 Apr 2017; median duration of treatment of 1666.0 days (range of 52-2052)

Time to PSA response (PSA decline ≥ 80% from Baseline) is defined as the time interval from the first study drug dose to the first date a decline from Baseline in PSA level of 80% or greater was recorded. Time to response was estimated using the Kaplan-Meier method.

From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)

Time to PSA decline ≥ 90% is defined as the time interval from the first study drug dose to the first date a decline from Baseline in PSA level of 90% or greater was recorded. Time to PSA decline ≥ 90% was estimated using the Kaplan-Meier method.

From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)

Time to PSA ≤ 4 ng/ml is defined as the time interval from the first study drug dose to the first date a decline in PSA to a result of 4 ng/ml or below was recorded. Time to PSA ≤ 4 ng/ml was estimated using the Kaplan-Meier method.

From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)

Time to PSA ≤ 0.1 ng/ml is defined as the time interval from the first study drug dose to the first date a decline in PSA to a result of 0.1 ng/ml or below was recorded. Time to PSA ≤ 0.1 ng/ml was estimated using the Kaplan-Meier method.

From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)

Time to PSA progression is defined as the time interval from the first study drug dose to the first date of PSA progression. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir unless the PSA next measurement(s), if available, does not confirm the PSA progression.

From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)

PSA doubling time was to be calculated from the slope estimated from a linear regression of the natural log of PSA fitted on time, if the slope was positive. Since the slope was negative for all participants, PSA doubling time could not be calculated.

Inclusion Criteria: Histologically confirmed prostate cancer (all stages) for whom androgen deprivation therapy is indicated (except when indicated in a neoadjuvant/adjuvant therapy) Asymptomatic from prostate cancer Non-castrate level of testosterone (≥ 8 nmol/L (230 ng/dL)) at screening PSA ≥ 2 ng/mL at screening Exclusion Criteria: Has previously or is currently receiving: Hormonal therapy with intent to treat prostate cancer Systemic glucocorticoids Chemotherapy with the intent to treat prostate cancer Opiate analgesics for pain from prostate cancer Radiation therapy for treatment of the primary tumor or metastases Has history of known or suspected brain or skull metastases or leptomeningeal disease Has history of seizure including febrile seizure or any condition that may predispose to seizure or history of loss of consciousness or transient ischemic attack Clinically significant cardiovascular disease

Trump D. Commentary on: "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study." Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR. Institut de Recherche Clinique, Universite Catholique de Louvain, Brussels, Belgium. Electronic address: bertrand.tombal@uclouvain.be. Aarhus University Hospital, Aarhus, Denmark. Herlev Hospital, Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. UZ Leuven, Leuven, Belgium. Klinik und Poliklinik fur Urologie, RWTH University Aachen, Aachen, Germany. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. UZ Brussel, Brussels, Belgium. Univerzita Karlova v Praze, Prague, Czech Republic. Astellas Pharma Global Development, Leiden, Netherlands. Astellas Pharma Global Development, Northbrook, IL, USA. Medivation Inc, San Francisco, CA, USA. Massachusetts General Hospital Cancer Center, Boston, MA, USA: Lancet Oncol. 2014 May;15(6):592-600; doi: 10.1016/S1470-2045(14)70129-9. [Epub 2014 Apr 14]. Urol Oncol. 2016 May;34(5):248-9. doi: 10.1016/j.urolonc.2015.03.012. Epub 2015 Apr 30.

Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Baron B, Hirmand M, Smith MR. Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naive Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Eur Urol. 2015 Nov;68(5):787-94. doi: 10.1016/j.eururo.2015.01.027. Epub 2015 Feb 14.

Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR. Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Lancet Oncol. 2014 May;15(6):592-600. doi: 10.1016/S1470-2045(14)70129-9. Epub 2014 Apr 14.