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Clinical characteristics associated with falls in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide

Prostate Cancer and Prostatic Diseases volume 26, pages 156–161 (2023)Cite this article

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A Correction to this article was published on 24 August 2023

This article has been updated

Abstract

Background

The phase III SPARTAN study demonstrated that apalutamide significantly improves metastasis-free survival and overall survival vs. placebo in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). However, patients receiving apalutamide experienced falls more frequently vs. those receiving placebo (15.6% vs. 9.0%).

Methods

806 patients with nmCRPC randomized to apalutamide in SPARTAN and treated with apalutamide in addition to ongoing androgen deprivation therapy (ADT) were included in this post-hoc analysis investigating clinical variables associated with a subsequent fall. Time to a fall was assessed with Cox proportional-hazards models adjusted for baseline characteristics and time-varying factors. Statistical inference was based on final multivariable models.

Results

Falls were reported for 125/803 (15.6%) patients treated with apalutamide and ADT. Most falls were grade 1 or 2 and did not require hospitalization. Median time from randomization to first fall was 9.2 months (range 0.1–25.3 months). In the final multivariable model of both baseline and after-baseline covariates, baseline patient characteristics (older age, poor Eastern Cooperative Oncology Group performance status, history of neuropathy, and α-blocker use before study treatment) remained significantly associated with fall; after-baseline clinical characteristics significantly associated with time to fall were development of neuropathy, arthralgia, and weight loss before fall.

Conclusions

This analysis identified risk factors for fall among nmCRPC patients treated with apalutamide. Clinical management can minimize these identified risks while enhancing patient outcomes. Preventive interventions should be considered when the identified baseline conditions and post-treatment neuropathy, arthralgia, or weight decrease are present, to reduce risk of fall.

Trial registration

ClinicalTrials.gov: NCT01946204

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Fig. 1: Time to treatment-emergent fall by number of baseline risk factors.
Fig. 2: Fall risk screening diagram.

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Data availability

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.

Change history

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Acknowledgements

Editorial assistance was provided by Tamara Fink, PhD, and Gwendolyn Elphick, PhD, of Parexel.

Funding

The SPARTAN study was funded by Janssen Research & Development. Funding for editorial assistance was provided by Janssen Global Services, LLC.

Author information

Author notes

  1. YaoYao Pollock

    Present address: St. Joseph Health Medical Group, Providence St. Joseph Health, Santa Rosa, CA, USA

Authors and Affiliations

  1. The Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA

    YaoYao Pollock & Eric J. Small

  2. Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA

    Matthew R. Smith

  3. Centre Hospitalier de l’Université de Montréal, Université de Montréal, Montréal, QC, Canada

    Fred Saad

  4. Guy’s, King’s and St. Thomas’ Hospitals, Great Maze Pond, London, UK

    Simon Chowdhury

  5. Georges Pompidou Hospital, University de Paris, Paris, France

    Stéphane Oudard

  6. University of Duisburg-Essen, Essen, and Ruprecht-Karls-University Heidelberg, Heidelberg, Germany

    Boris Hadaschik

  7. Spanish National Cancer Research Centre (CNIO), Madrid and Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain

    David Olmos

  8. Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Ji Youl Lee

  9. Yokohama City University Medical Center, Yokohama, Japan

    Hiroji Uemura

  10. Janssen Research & Development, Titusville, NJ, USA

    Amitabha Bhaumik & Anil Londhe

  11. Janssen Research & Development, High Wycombe, UK

    Brendan Rooney

  12. Janssen Research & Development, Los Angeles, CA, USA

    Sabine D. Brookman-May

  13. Ludwig-Maximilians-University, Munich, Germany

    Sabine D. Brookman-May

  14. Janssen Research & Development, Beerse, Belgium

    Peter De Porre

  15. Janssen Research & Development, Raritan, NJ, USA

    Suneel D. Mundle

Authors
  1. YaoYao Pollock
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Contributions

Conception, design, and drafting of the manuscript: YP, EJS, AL, SDM, SB-M, PDP, BR; Conception, design, acquisition of data, statistical analysis, and drafting of the manuscript: AB. All authors contributed to analysis and interpretation of the data and critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to YaoYao Pollock.

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Competing interests

MRS reports travel expenses from and an advisory role for Amgen; research funding and travel expenses from and an advisory role for Bayer; research funding and travel expenses from and an advisory role for Janssen; travel expenses and an advisory role for Lilly; and an advisory role for Novartis and Pfizer. FS reports honoraria from AbbVie and Amgen; consultancy for and research funding and honoraria from Astellas, AstraZeneca/MedImmune, Bayer, Janssen, and Sanofi; and research funding from Bristol Myers Squibb and Pfizer. SC reports consultancy and speakers bureau participation for and honoraria and travel expenses from Astellas Pharma, Bayer, Beigene, Clovis Oncology, Janssen-Cilag, Johnson & Johnson, Novartis, and Sanofi; and research funding from Clovis Oncology. SO reports consultancy for and honoraria from Astellas; consultancy for and travel expenses and honoraria from Bayer, Bristol Myers Squibb, Eisai Merck, Sharp & Dohme, Novartis, and Pfizer; research funding from Ipsen; consultancy for and honoraria from Janssen; and consultancy for and research funding and honoraria from Sanofi. BH reports research funding from German Cancer Aid and the German Research Foundation; consultancy for and research funding and travel expenses from Janssen; consultancy for and travel expenses from Astellas and Bayer; research funding and royalties from Uromed; and consultancy for ABX, Pfizer, and Lightpoint Medical, Inc. DO reports advisory roles for AstraZeneca, Bayer, Clovis Oncology, Daiichi-Sankyo, Janssen, MSD, and Genentech/Roche; compensation for travel from Bayer, Ipsen, Janssen, and Genentech/Roche; honoraria from Bayer, Janssen, and Sanofi; and research funding from Astellas, AstraZeneca, Bayer, Genentech/Roche, Janssen, Pfizer, Medivation, MSD, and Pfizer. HU reports honoraria and travel expenses from Janssen; honoraria from Astellas; consultancy for and honoraria and travel expenses from Takeda; honoraria and travel expenses from Sanofi and Bayer; and consultancy for AstraZeneca. EJS reports an advisory role for and stock in Fortis; stock in Harpoon Therapeutics; honoraria for speaking engagements and an advisory role for Janssen; honoraria from Johnson & Johnson for speaking engagements; and consultancy or as an advisory board member for Teon Therapeutics, Ultragenyx, Beigene, and Tolero. AB, AL, BR, SB-M, PD, and SDM report that they are employees of Janssen and hold stock in Johnson & Johnson. JYL and YP have no conflicts to disclose.

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The original online version of this article was revised: In this article the affiliation details for Author Ji Youl Lee were incorrectly given as St. 'Mary’s Hospital of Catholic University, Seoul, South Korea.' but should have been 'Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.' The original article has been corrected.

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Pollock, Y., Smith, M.R., Saad, F. et al. Clinical characteristics associated with falls in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide. Prostate Cancer Prostatic Dis 26, 156–161 (2023). https://doi.org/10.1038/s41391-022-00592-9

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