Clinical characteristics associated with falls in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide.
Journal
Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
30
09
2021
accepted:
31
08
2022
revised:
05
08
2022
pubmed:
9
10
2022
medline:
22
3
2023
entrez:
8
10
2022
Statut:
ppublish
Résumé
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%). 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. 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. 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. ClinicalTrials.gov: NCT01946204.
Sections du résumé
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.
Identifiants
pubmed: 36209239
doi: 10.1038/s41391-022-00592-9
pii: 10.1038/s41391-022-00592-9
doi:
Substances chimiques
apalutamide
0
Androgen Receptor Antagonists
0
Androgen Antagonists
0
Banques de données
ClinicalTrials.gov
['NCT01946204']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
156-161Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
ERLEADA (apalutamide) [prescribing information]. Janssen Pharmaceutical Companies, Horsham, PA; 2020.
ERLEADA (apalutamide). [Summary of Product Characteristics]. The electronic Medicines Compendium (eMC) Web site ( https://www.ema.europa.eu/en/documents/product-information/erleada-epar-product-information_en.pdf ) and https://www.ema.europa.eu/en/medicines/human/EPAR/erleada .
Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide and overall survival in prostate cancer. Eur Urol. 2021;79:150–8.
doi: 10.1016/j.eururo.2020.08.011
pubmed: 32907777
Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N. Engl J Med. 2018;378:1408–18.
doi: 10.1056/NEJMoa1715546
pubmed: 29420164
Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, et al. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19:1404–16.
doi: 10.1016/S1470-2045(18)30456-X
pubmed: 30213449
Oudard S, Hadaschik BA, Saad F, Cella D, Basch E, Mainwaring PN, et al. Health-related quality of life (HRQoL) at final analysis of the SPARTAN study of apalutamide (APA) vs placebo (PBO) in patients (pts) with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen deprivation therapy (ADT). Ann Oncol. 2020;31:S521. 632P
doi: 10.1016/j.annonc.2020.08.891
Myint ZW, Momo HD, Otto DE, Yan D, Wang P, Kolesar JM. Evaluation of fall and fracture risk among men with prostate cancer treated with androgen receptor inhibitors: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2025826.
doi: 10.1001/jamanetworkopen.2020.25826
pubmed: 33201234
pmcid: 7672516
Hussain S, Breunis H, Timilshina N, Alibhai S. Falls in men on androgen deprivation therapy for prostate cancer. J Geriatr Oncol. 2010;1:32–39.
doi: 10.1016/j.jgo.2010.03.004
Winters-Stone KM, Moe E, Graff JN, Dieckmann NF, Stoyles S, Borsch C, et al. Falls and frailty in prostate cancer survivors: current, past, and never users of androgen deprivation therapy. J Am Geriatr Soc. 2017;65:1414–9.
doi: 10.1111/jgs.14795
pubmed: 28263373
pmcid: 5507739
Wu FJ, Sheu SY, Lin HC, Chung SD. Increased fall risk in patients receiving androgen deprivation therapy for prostate cancer. Urology. 2016;95:145–50.
doi: 10.1016/j.urology.2016.05.058
pubmed: 27318262
Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol. 2019;30:1813–20.
doi: 10.1093/annonc/mdz397
pubmed: 31560066
pmcid: 6927320
Panel on Prevention of Falls in Older Persons, American Geriatrics Society, British Geriatrics Society. Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc. 2011;59:148–57.
doi: 10.1111/j.1532-5415.2010.03234.x
National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v4.0. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40 .
Burns E, Kakara R. Deaths from falls among persons aged ≥65 years—United States, 2007-2016. MMWR Morb Mortal Wkly Rep. 2018;67:509–14.
doi: 10.15585/mmwr.mm6718a1
pubmed: 29746456
pmcid: 5944976
Toomey A, Friedman L. Mortality in cancer patients after a fall-related injury: the impact of cancer spread and type. Injury. 2014;45:1710–6.
doi: 10.1016/j.injury.2014.03.008
pubmed: 24745652
Sterling DA, O’Connor JA, Bonadies J. Geriatric falls: injury severity is high and disproportionate to mechanism. J Trauma. 2001;50:116–9.
doi: 10.1097/00005373-200101000-00021
pubmed: 11231681
Bergen G, Stevens MR, Burns ER. Falls and fall injuries among adults aged ≥65 years—United States, 2014. MMWR Morb Mortal Wkly Rep. 2016;65:993–8.
doi: 10.15585/mmwr.mm6537a2
pubmed: 27656914
Centers for Disease Control and Prevention. Older adult falls: important facts about falls. https://www.cdc.gov/homeandrecreationalsafety/falls/adultfalls.html .
Tinetti ME, Gordon C, Sogolow E, Lapin P, Bradley EH. Fall-risk evaluation and management: challenges in adopting geriatric care practices. Gerontologist. 2006;46:717–25.
doi: 10.1093/geront/46.6.717
pubmed: 17169927
Wildes TM, Dua P, Fowler SA, Miller JP, Carpenter CR, Avidan MS, et al. Systematic review of falls in older adults with cancer. J Geriatr Oncol. 2015;6:70–83.
doi: 10.1016/j.jgo.2014.10.003
pubmed: 25454770
Huang MH, Blackwood J, Godoshian M, Pfalzer L. Factors associated with self-reported falls, balance or walking difficulty in older survivors of breast, colorectal, lung, or prostate cancer: results from Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey linkage. PLoS One. 2018;13:e0208573.
doi: 10.1371/journal.pone.0208573
pubmed: 30566443
pmcid: 6300321
Mohile SG, Fan L, Reeve E, Jean-Pierre P, Mustian K, Peppone L, et al. Association of cancer with geriatric syndromes in older Medicare beneficiaries. J Clin Oncol. 2011;29:1458–64.
doi: 10.1200/JCO.2010.31.6695
pubmed: 21402608
pmcid: 3082984
Guerard EJ, Deal AM, Williams GR, Jolly TA, Nyrop KA, Muss HB. Falls in older adults with cancer: evaluation by oncology providers. J Oncol Pr. 2015;11:470–4.
doi: 10.1200/JOP.2014.003517
Centers for Disease Control and Prevention. Algorithm for fall risk screening, assessment, and intervention. https://www.cdc.gov/steadi/pdf/STEADI-Algorithm-508.pdf .
Stone CA, Lawlor PG, Savva GM, Bennett K, Kenny RA. Prospective study of falls and risk factors for falls in adults with advanced cancer. J Clin Oncol. 2012;30:2128–33.
doi: 10.1200/JCO.2011.40.7791
pubmed: 22585687
Vande Walle N, Kenis C, Heeren P, Van Puyvelde K, Decoster L, Beyer I, et al. Fall predictors in older cancer patients: a multicenter prospective study. BMC Geriatr. 2014;14:135.
doi: 10.1186/1471-2318-14-135
pubmed: 25511244
pmcid: 4320446
Williams GR, Deal AM, Nyrop KA, Pergolotti M, Guerard EJ, Jolly TA, et al. Geriatric assessment as an aide to understanding falls in older adults with cancer. Support Care Cancer. 2015;23:2273–80.
doi: 10.1007/s00520-014-2598-0
pubmed: 25576434
pmcid: 4484313