ASCO 2018: Results from the PROSPER Study: HRQoL Deterioration and Pain Progression in Men with Non-Metastatic Castration-Resistant Prostate Cancer

Chicago, IL (UroToday.com) At the 2018 GU ASCO meeting in San Francisco, Maha Hussain, MD presented the results of PROSPER, a phase III randomized controlled trial assigning 1,401 men with non-metastatic CRPC (M0 CRPC) 2:1 to enzalutamide (160 mg) or placebo [1]. With a primary endpoint of metastasis-free survival (MFS), enzalutamide had a significantly longer time to metastasis (36.6 months, 95%CI 33.1-NR) compared to placebo (14.7 months, 95%CI 14.2-15.0; HR 0.29, 95%CI 0.24-0.35).  Secondary endpoints also favored enzalutamide including:
  • Time to first use of new antineoplastic therapy (39.6 months vs 17.7 months; HR 0.21, 95%CI 0.17-0.26)
  • Time to PSA progression (37.2 months vs 3.9 months; HR 0.07, 95%CI 0.05-0.08)
During this year's 2018 ASCO annual meeting, Gerhardt Attard, MD, and colleagues presented results of the Health-related quality of life (HRQoL) and pain evaluations among men in the PROSPER trial.

Eligibility for enrollment in PROSPER included:

  • M0 CRPC
  • PSA doubling time ≤10 months
  • PSA ≥2 ng/mL
  • Continued ADT
Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory, Short Form, were used to assess HRQoL and pain at baseline and every 16 weeks during treatment. The authors defined pain progression as ≥2 points in pain severity items and mean scores increase from baseline. HRQoL improvement/deterioration as an increase/decrease from baseline included using pre-established thresholds for clinically meaningful differences. Time to first confirmed (at two consecutive visits) and unconfirmed HRQoL deterioration/pain progression were assessed using Kaplan-Meier estimates and Cox proportional hazards models.

Baseline characteristics and scores were similar between the enzalutamide and placebo arms with low pain (median 0) and high HRQoL (median FACT-P total score: 121). The decrease in attrition rate was greater in the placebo arm (53%) compared to the enzalutamide arm (68%), mainly due to disease progression (at week 49). Most patients reported no change or improvement in HRQoL. The proportion of patients with pain progression at week 49 was similar between those receiving enzalutamide (11–20%) and placebo (14–21%). There was a non-statistically significant lower risk of pain progression observed with enzalutamide vs. placebo in the confirmed analysis (HR 0.78–0.93, p > 0.05). Furthermore, there was a statistically significant lower risk of deterioration observed for patients receiving enzalutamide for FACT-P total (HR 0.83, 95%CI 0.69-0.99), FACT Advanced Prostate Symptom Index (HR 0.79, 95%CI 0.65-0.94), prostate cancer subscale (HR 0.79, 95%CI 0.67-0.93), and emotional well-being (HR 0.69, 95%CI 0.55-0.86) in the confirmed analyses.

With the significantly improved MFS rates reported in PROSPER, as well as similar outcomes in SPARTAN (apalutamide) [2], we now have several options for treating patients in the M0 CRPC disease space. Based on the results presented here, patients receiving enzalutamide in the PROSPER trial had no worsening of HRQoL and significantly reduced the risk of clinically meaningful HRQoL deterioration in several FACT-P domains. Clinical trial information: NCT02003924


Presented by: Gerhardt Attard, MD, FRCP, Ph.D., The Institute of Cancer Research and the Royal Marsden, Surrey, United Kingdom

Co-Authors: Fred Saad, Bertrand F. Tombal, Maha Hussain, Cora N. Sternberg, De Phung, Shevani Naidoo, Katharina Modelska, Arlene Reisman, Cristina Ivanescu, David F. Penson; Hospitalier de l’Université de Montréal/CRCHUM, Montreal, QC, Canada; Cliniques Universitaires Saint-Luc, Brussels, Belgium; Northwestern University Robert H. Lurie Comprehensive Cancer Center, Chicago, IL; San Camillo Forlanini Hospital, Rome, Italy; Astellas Pharma Inc., Leiden, Netherlands; Astellas Pharma Inc., Chertsey, United Kingdom; Pfizer, Inc., San Francisco, CA, US; Pfizer Inc., New York, NY; IQVIA, Amsterdam-Zuidoost, Netherlands; Vanderbilt University Medical Center, Nashville, TN


References:
1. Hussain M, Fizazi K, Saad F, et al. PROSPER: A phase 3, randomized, double-blind, placebo-controlled study of enzalutamide in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC). J Clin Oncol 2018;36(suppl 6S;abstr 3).
2. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA

Further Related Content:
Watch: Meeting an Unmet Need in the Nonmetastatic Castration-Resistant Prostate Cancer Patient Population - Maha Hussain
Watch: Changing the Standard of Care in the M0 CRPC Patient: PROSPER - A Conversation with Cora Sternberg
Watch: The Incredible Shrinking M0 CRPC - Phillip Koo

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