Impact of enzalutamide on patient-reported fatigue in patients with prostate cancer: data from the pivotal clinical trials.
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:
02 2022
02 2022
Historique:
received:
30
04
2021
accepted:
19
08
2021
revised:
12
08
2021
pubmed:
15
9
2021
medline:
14
6
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
Fatigue is a multifactorial symptom commonly reported by patients with prostate cancer as a result of disease and treatment. This study assesses the impact enzalutamide has on patient-reported fatigue ("fatigue") by using patient-reported outcomes from four pivotal, placebo-controlled trials of enzalutamide (ARCHES (NCT02677896), PROSPER (NCT02003924), PREVAIL (NCT01212991), and AFFIRM (NCT00974311)). Fatigue was assessed in the individual studies using the Functional Assessment of Cancer Therapy-Prostate item GP1 at baseline, weeks 13 or 17, and every 12 weeks until disease progression. Longitudinal changes were assessed using mean scores and mixed-model repeated measures. The fatigue rates at baseline were higher in patients with later-stage disease (metastatic and/or castration-resistant prostate cancer (CRPC)) and among patients who had already received prior treatment lines; rates ranged between 58% in PROSPER (nonmetastatic CRPC) and 86% in AFFIRM (post-docetaxel metastatic CRPC). Irrespective of disease state, initiation of enzalutamide or placebo resulted in an early increase of fatigue (by weeks 13 or 17), with fatigue levels stabilizing thereafter. At last assessment, ≥55% of patients reported fatigue improvement or stabilization in all trials compared to baseline. More patients reported fatigue worsening by ≥1 or ≥2 units with enzalutamide plus androgen deprivation therapy (ADT) than with placebo plus ADT in ARCHES, PROSPER, and PREVAIL, but the between-group difference was <10% in all trials. The levels of fatigue were greater in mCRPC and lower in earlier states of disease. In all trials, patients reported a small increase in fatigue for the first 13-17 weeks after starting enzalutamide or placebo, with slightly greater fatigue with enzalutamide in all studies except AFFIRM, but fatigue stabilized or improved thereafter. This suggests a role for clinical management of fatigue to help patients cope early in treatment.
Sections du résumé
BACKGROUND
Fatigue is a multifactorial symptom commonly reported by patients with prostate cancer as a result of disease and treatment. This study assesses the impact enzalutamide has on patient-reported fatigue ("fatigue") by using patient-reported outcomes from four pivotal, placebo-controlled trials of enzalutamide (ARCHES (NCT02677896), PROSPER (NCT02003924), PREVAIL (NCT01212991), and AFFIRM (NCT00974311)).
METHODS
Fatigue was assessed in the individual studies using the Functional Assessment of Cancer Therapy-Prostate item GP1 at baseline, weeks 13 or 17, and every 12 weeks until disease progression. Longitudinal changes were assessed using mean scores and mixed-model repeated measures.
RESULTS
The fatigue rates at baseline were higher in patients with later-stage disease (metastatic and/or castration-resistant prostate cancer (CRPC)) and among patients who had already received prior treatment lines; rates ranged between 58% in PROSPER (nonmetastatic CRPC) and 86% in AFFIRM (post-docetaxel metastatic CRPC). Irrespective of disease state, initiation of enzalutamide or placebo resulted in an early increase of fatigue (by weeks 13 or 17), with fatigue levels stabilizing thereafter. At last assessment, ≥55% of patients reported fatigue improvement or stabilization in all trials compared to baseline. More patients reported fatigue worsening by ≥1 or ≥2 units with enzalutamide plus androgen deprivation therapy (ADT) than with placebo plus ADT in ARCHES, PROSPER, and PREVAIL, but the between-group difference was <10% in all trials.
CONCLUSIONS
The levels of fatigue were greater in mCRPC and lower in earlier states of disease. In all trials, patients reported a small increase in fatigue for the first 13-17 weeks after starting enzalutamide or placebo, with slightly greater fatigue with enzalutamide in all studies except AFFIRM, but fatigue stabilized or improved thereafter. This suggests a role for clinical management of fatigue to help patients cope early in treatment.
Identifiants
pubmed: 34518652
doi: 10.1038/s41391-021-00447-9
pii: 10.1038/s41391-021-00447-9
pmc: PMC9184276
doi:
Substances chimiques
Androgen Antagonists
0
Benzamides
0
Nitriles
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
Banques de données
ClinicalTrials.gov
['NCT01212991', 'NCT00974311']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
288-295Informations de copyright
© 2021. The Author(s).
Références
Tomaszewski EL, Moise P, Krupnick RN, Downing J, Meyer M, Naidoo S, et al. Symptoms and impacts in non-metastatic castration-resistant prostate cancer: qualitative study findings. Patient. 2017;10:567–78.
doi: 10.1007/s40271-017-0227-y
Holmstrom S, Naidoo S, Turnbull J, Hawryluk E, Paty J, Morlock R. Symptoms and Impacts in metastatic castration-resistant prostate cancer: qualitative findings from patient and physician interviews. Patient. 2019;12:57–67.
doi: 10.1007/s40271-018-0349-x
Nussbaum N, George DJ, Abernethy AP, Dolan CM, Oestreicher N, Flanders S, et al. Patient experience in the treatment of metastatic castration-resistant prostate cancer: state of the science. Prostate Cancer Prostatic Dis. 2016;19:111–21.
doi: 10.1038/pcan.2015.42
Pirl WF, Greer JA, Goode M, Smith MR. Prospective study of depression and fatigue in men with advanced prostate cancer receiving hormone therapy. Psychooncology. 2008;17:148–53.
doi: 10.1002/pon.1206
Stone P, Hardy J, Huddart R, A’Hern R, Richards M. Fatigue in patients with prostate cancer receiving hormone therapy. Eur J Cancer. 2000;36:1134–41.
doi: 10.1016/S0959-8049(00)00084-8
Nelson AM, Gonzalez BD, Jim HS, Cessna JM, Sutton SK, Small BJ, et al. Characteristics and predictors of fatigue among men receiving androgen deprivation therapy for prostate cancer: a controlled comparison. Support Care Cancer. 2016;24:4159–66.
doi: 10.1007/s00520-016-3241-z
Abiraterone US package insert. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202379s027s028lbl.pdf . Accessed: April 2021.
Enzalutamide US package insert. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213674s000lbl.pdf . Accessed: April 2021.
Apalutamide US package insert. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210951s003lbl.pdf . Accessed: April 2021.
Docetaxel US package insert. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022534s011lbl.pdf . Accessed: April 2021.
Darolutamide US package insert. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212099Orig1s000lbl.pdf . Accessed: April 2021.
Radium-223 US package insert. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203971s016lbl.pdf . Accessed: April 2021.
Cabazitaxel EPAR. 2020. https://www.ema.europa.eu/en/documents/product-information/cabazitaxel-accord-epar-product-information_en.pdf . Accessed: April 2021.
Olaparib US package insert. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206162s011lbl.pdf . Accessed: April 2021.
Fromme EK, Eilers KM, Mori M, Hsieh YC, Beer TM. How accurate is clinician reporting of chemotherapy adverse effects? A comparison with patient-reported symptoms from the Quality-of-Life Questionnaire C30. J Clin Oncol. 2004;22:3485–90.
doi: 10.1200/JCO.2004.03.025
Basch EM, McDonough T, Iasonos A, Siegel E, Culkin A, Kris M, et al. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events. J Clin Oncol. 2006;24(Suppl 18):8515.
doi: 10.1200/jco.2006.24.18_suppl.8515
Drago JZ, Gönen M, Thanarajasingam G, Sacks CA, Morris MJ, Kantoff PW, et al. Inferences about drug safety in phase 3 trials in oncology: examples from advanced prostate cancer. J Natl Cancer Inst. 2021;113:553–61. https://doi.org/10.1093/jnci/djaa134 .
Barsevick AM, Cleeland CS, Manning DC, O’Mara AM, Reeve BB, Scott JA, et al. ASCPRO recommendations for the assessment of fatigue as an outcome in clinical trials. J Pain Symptom Manag. 2010;39:1086–99.
doi: 10.1016/j.jpainsymman.2010.02.006
Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37:2974–86.
doi: 10.1200/JCO.19.00799
Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2020;382:2197–206.
doi: 10.1056/NEJMoa2003892
Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33.
doi: 10.1056/NEJMoa1405095
Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.
doi: 10.1056/NEJMoa1207506
Esper P, Mo F, Chodak G, Sinner M, Cella D, Pienta KJ. Measuring quality of life in men with prostate cancer using the Functional Assessment of Cancer Therapy-prostate instrument. Urology. 1997;50:920–8.
doi: 10.1016/S0090-4295(97)00459-7
Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74.
doi: 10.1056/NEJMoa1800536
Ganguli ARK, Turnbull J, Bhadauria H, Ivanescu C, Tombal B. PCN278 correlation between the Brief Fatigue Inventory (BFI) and Functional Assessment of Cancer Therapy–Prostate (FACT-P) to measure fatigue in men with metastatic castration-resistant prostate cancer (mCRPC). Value Health. 2020;23 (Suppl 1):S72.
doi: 10.1016/j.jval.2020.04.1744
Stenzl A, De Giorgi U, Alekseev B, Iguchi T, Szmulewitz RZ, Flaig TW, et al. The impact of enzalutamide on quality of life in men with metastatic hormone-sensitive prostate cancer based on prior therapy, risk, and symptom subgroups. Submitted.
Tombal B, Saad F, Penson D, Hussain M, Sternberg CN, Morlock R, et al. Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20:556–69.
doi: 10.1016/S1470-2045(18)30898-2
Loriot Y, Miller K, Sternberg CN, Fizazi K, de Bono JS, Chowdhury S, et al. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol. 2015;16:509–21.
doi: 10.1016/S1470-2045(15)70113-0
Cella D, Ivanescu C, Holmstrom S, Bui CN, Spalding J, Fizazi K. Impact of enzalutamide on quality of life in men with metastatic castration-resistant prostate cancer after chemotherapy: additional analyses from the AFFIRM randomized clinical trial. Ann Oncol. 2015;26:179–85.
doi: 10.1093/annonc/mdu510
Moreh E, Jacobs JM, Stessman J. Fatigue, function, and mortality in older adults. J Gerontol A Biol Sci Med Sci. 2010;65:887–95.
doi: 10.1093/gerona/glq064
Fabi A, Bhargava R, Fatigoni S, Guglielmo M, Horneber M, Roila F, et al. Cancer-related fatigue: ESMO Clinical Practice Guidelines for diagnosis and treatment. Ann Oncol. 2020;31:713–23.
doi: 10.1016/j.annonc.2020.02.016