ASCO GU 2018: First Presentation - PROSPER: Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)

San Francisco, CA ( Dr. Maha Hussain provided the first presentation of the phase III randomized double-blind controlled trial, the following men were eligible for inclusion:

  • cM0 CRPC (central review)
  • Rising PSA despite castration-resistant testosterone (testosterone <= 50 ng/dL)
  • Baseline PSA >= 2 ng/mL
  • PSADT <= 10 months
Patients were stratified by the following:

1) PSADT: PSADT <6 months and 6-10 months)
2) Use of bone-targeted agents at baseline: Yes vs. No

Their endpoints were as follows:

Primary endpoint: Metastasis-free survival (defined as time from randomization to radiographic progression or death within 112 days of treatment discontinuation)

Secondary endpoints:

  • Safety
  • Time to PSA Progression
  • Time to use of new antineoplastic therapy
  • Overall survival
  • PSA response
  • Quality of Life
They were able to recruit 1401 total patients across all the institutions. Men were randomized in a 2:1 fashion to either enzalutamide (ENZA) 160 mg daily + ADT or placebo + ADT. 

Demographics of the patient populations – both groups were evenly balanced. Some key points, as highlighted by Dr. Hussain:

  • Median age for the group was 73 and 74 (but patients as old as 90+ were included)
  • Median serum PSA was 11
  • Median PSADT was actually 3.6 & 3.8 – well below the cutoff of 10! 
  • In fact, 75% of both groups fell in the PSADT < 6 months stratification
  • Median duration of therapy was 18.4 months (Enza) vs. 11.1 months (placebo)
First, she focused on the adverse event profiles. Serious Grade 3+ adverse events were higher in the ENZA group (31% vs. 23%), and the most common ones were hypertension, fatigue and hematuria. Patients on enzalutamide discontinued treatment due to adverse events as a slightly higher rate (9% vs. 6%) and had a slightly higher mortality rate (3% vs. 1%). 

Looking at clinical outcomes, she first addressed progression. Progression in the ENZA arm was 50% that of the placebo arm – 219 events in 933 patients (23%) vs. 228 events in 468 patients (49%). However, she also pointed out briefly that there was a 15% mortality rate (death without documented progression) in the ENZA arm, compared to 2% in the placebo arm.  The 15% specifically refers to patients on the enzalutamide arm who progressed in the metastasis free survival (MFS) analysis population, due to death, rather than radiographic progression.  There were 219 progression events in the enzalutamide + ADT arm, 187 (85%) of which were due to radiographic progression and 32 (15%) due to death during treatment or up to 112 days after treatment discontinuation.

Focusing on the primary endpoint, MFS – the Kaplan-Meier curve split very early, and there was a 71% risk reduction in MFS favoring enzalutamide. Median MFS was 36.6 months vs. 14.7 months (placebo), HR 0.29, p<0.0001. The benefit was seen in all subgroup analyses. 

Similar findings were identified for all secondary endpoints, including time to PSA progression and time to first use of new antineoplastic agent (Table 1). Overall survival, as mentioned above, was an interim analysis – median follow-up was 22 months for each arm. While there was a 20% risk reduction in OS, the p-value was 0.1519 – trending towards significant, but not yet significant. The curves do begin to split on the Kaplan-Meier survival analysis. 

Summary of SPARTAN and PROSPER Studies (Table 1)
PROSPER Copyright UroToday

Presented by: Maha Hussain, MD, FACP, FASCO, Northwestern University, Chicago, IL

Authors: Maha Hussain, Karim Fizazi, Fred Saad, Per Rathenborg, Neal D. Shore, Eren Demirhan, Katharina Modelska, De Phung, Andrew Krivoshik, Cora N. Sternberg

Author Affiliation(s): Northwestern University, Chicago, IL; Institut Gustave Roussy, University of Paris Sud, Cancer Medicine, Villejuif, France; Centre Hospitalier de l’Université de Montréal/CRCHUM, Montreal, QC, Canada; Herlev Hospital, Herlev, Denmark; Carolina Urologic Research Center, Myrtle Beach, SC; Pfizer, Inc., San Francisco, CA; Pfizer, Inc., San Francisco, CA, US; Astellas Pharma Inc., Leiden, Netherlands; Astellas Pharma Inc., Northbrook, IL; San Camillo Forlanini Hospital, Rome, Italy

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto | @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

Read More:

Watch: Changing the Standard of Care in the M0 CRPC Patient: PROSPER - A Conversation with Cora Sternberg

Cora Sternberg's EAU 2018 Presentation:Prostate-Specific Antigen Response in Men with Nonmetastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide: Results from PROSPER

Watch: Meeting an Unmet Need in the Non-Metastatic Castration Resistant Prostate Cancer Patient Population - Maha Hussain