Post Hoc Analysis of Rapid and Deep Prostate-specific Antigen Decline and Patient-reported Health-related Quality of Life in SPARTAN and TITAN Patients with Advanced Prostate Cancer

Eric J Small; Kim N Chi; Simon Chowdhury; Katherine B Bevans; Amitabha Bhaumik; Fred Saad; Byung Ha Chung; Lawrence I Karsh; Stéphane Oudard; Peter De Porre; Sabine D Brookman-May; Sharon A McCarthy; Suneel D Mundle; Hirotsugu Uemura; Matthew R Smith; Neeraj Agarwal

doi:10.1016/j.euo.2023.11.015

Post Hoc Analysis of Rapid and Deep Prostate-specific Antigen Decline and Patient-reported Health-related Quality of Life in SPARTAN and TITAN Patients with Advanced Prostate Cancer

Eur Urol Oncol. 2023 Dec 9:S2588-9311(23)00280-8. doi: 10.1016/j.euo.2023.11.015. Online ahead of print.

Authors

Eric J Small¹, Kim N Chi², Simon Chowdhury³, Katherine B Bevans⁴, Amitabha Bhaumik⁵, Fred Saad⁶, Byung Ha Chung⁷, Lawrence I Karsh⁸, Stéphane Oudard⁹, Peter De Porre¹⁰, Sabine D Brookman-May¹¹, Sharon A McCarthy¹², Suneel D Mundle¹², Hirotsugu Uemura¹³, Matthew R Smith¹⁴, Neeraj Agarwal¹⁵

Affiliations

¹ Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. Electronic address: eric.small@ucsf.edu.
² BC Cancer and Vancouver Prostate Centre, Vancouver, BC, Canada.
³ Guy's, King's, and St. Thomas' Hospitals and Sarah Cannon Research Institute, London, UK.
⁴ Janssen Global Commercial Strategy Organization, Horsham, PA, USA.
⁵ Janssen Research & Development, Titusville, NJ, USA.
⁶ Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
⁷ Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁸ The Urology Center of Colorado, Denver, CO, USA.
⁹ Georges Pompidou Hospital, Université Paris Descartes, Paris, France.
¹⁰ Janssen Research & Development, Beerse, Belgium.
¹¹ Ludwig-Maximilians-University, Munich, Germany; Janssen Research & Development, Spring House, PA, USA.
¹² Janssen Research & Development, Raritan, NJ, USA.
¹³ Kindai University Faculty of Medicine, Osaka, Japan.
¹⁴ Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA.
¹⁵ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

PMID: 38072759
DOI: 10.1016/j.euo.2023.11.015

Abstract

Background: Adding apalutamide to androgen-deprivation therapy (ADT) resulted in a rapid (at 3- and 6-mo treatment) and deep prostate-specific antigen (PSA) decline (to ≤0.2 ng/ml or ≥90% from baseline), improved overall survival, reduced risk of disease progression, and prolonged health-related quality of life (HRQoL) in nonmetastatic castration-resistant prostate cancer (nmCRPC) in SPARTAN and metastatic castration-sensitive PC (mCSPC) in TITAN.

Objective: To evaluate the association of a rapid, deep PSA decline at 3 and 6 mo achieved with the addition of apalutamide to ADT with patient-reported outcomes (PROs) in SPARTAN and TITAN.

Design, setting, and participants: A post hoc analysis of SPARTAN and TITAN PRO data was performed.

Intervention: Apalutamide versus placebo plus concurrent ADT.

Outcome measurements and statistical analysis: PROs were assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P; SPARTAN and TITAN), Brief Pain Inventory-Short Form (BPI-SF; TITAN), and Brief Fatigue Inventory (BFI; TITAN) at baseline, prespecified cycles during treatment, and after progression for ≤1 yr. The association between a deep PSA decline at landmark 3 or 6 mo of apalutamide and the time to worsening of PROs was assessed using the Kaplan-Meier methodology and Cox proportional-hazard modeling.

Results and limitations: Among 806 SPARTAN and 525 TITAN apalutamide-treated patients, the median treatment duration was 32.9 and 39.3 mo, respectively. Patients achieving a deep PSA decline at 3 mo had longer time to worsening in FACT-P total, FACT-P physical well-being, BPI-SF worst pain intensity, or BFI worst fatigue intensity. The 6-mo PSA decline results were similar. Limitations of patient characteristics in clinical studies should be considered.

Conclusions: Attaining a deep and rapid PSA decline at 3 mo with apalutamide plus ADT was associated with longer preservation of overall HRQoL and physical well-being in nmCRPC and mCSPC.

Patient summary: Quality of life is maintained in individuals with advanced prostate cancer who achieve a deep prostate-specific antigen decline at 3 mo of apalutamide plus drugs that lower male sex hormones.

Keywords: Apalutamide; Metastatic castration-sensitive prostate cancer; Nonmetastatic castration-resistant prostate cancer.