Abstract 665P
Background
This study examined the impact of enzalutamide (ENZA) vs. placebo (PBO) on self-reported fatigue across the prostate cancer disease continuum: metastatic [m]HSPC (ARCHES), nonmetastatic [nm]CRPC (PROSPER), mCRPC pre-chemo (PREVAIL), and mCRPC post-chemo (AFFIRM).
Methods
Fatigue was self-assessed by patients using the item “I have a lack of energy” (0-not at all to 4-very much) on the FACT-P tool. Longitudinal change from baseline to week 13 and week 13 to end of study was analyzed (mixed models repeated measures). Responder analysis was conducted to examine the proportion of patients improving or worsening in fatigue.
Results
At baseline, patients across the disease continuum reported comparable levels of fatigue. Across studies, patients in ENZA and PBO arms experienced worsening of fatigue up to week 13, except in AFFIRM. A numerically larger proportion of patients experienced clinically meaningful (≥2 point) worsening of fatigue with ENZA vs. PBO with differences between groups ranging from 3-9%, particularly in trials involving asymptomatic to minimally symptomatic patients at baseline (Table). In AFFIRM, which included more symptomatic patients, fewer experienced fatigue worsening (8.5% ENZA vs. 16.3% PBO) and more patients experienced improvements with ENZA vs. PBO (5.7% vs. 1.1%). Differences were less apparent between groups in a mean change analysis; however, responder analysis showed the majority of patients in both arms reported stable or improved fatigue across all disease states. Table: 665P
| Study | End of study, weeks | Arm | Least squares mean change | Responder analysis | ||
| Baseline to week 13* | Week 13* to end of study | Worsen ≥2 points, % | Improve ≥2 points, % | |||
| ARCHES | 73 | ENZA | 0.31 | 0.16 | 18.7 | 7.3 |
| PBO | 0.05 | 0.07 | 7.1 | 8.1 | ||
| PROSPER | 97 | ENZA | 0.64 | 0.25 | 14.7 | 3.4 |
| PBO | 0.35 | 0.49 | 10.0 | 4.4 | ||
| PREVAIL | 61 | ENZA | 0.42 | 0.36 | 12.5 | 2.1 |
| PBO | 0.49 | 0.40 | 9.6 | 4.3 | ||
| AFFIRM | 25 | ENZA | 0.31 | 0.03 | 8.5 | 5.7 |
| PBO | 0.52 | 0.29 | 16.3 | 1.1 |
*PROSPER: week 17 was used instead of week 13
Conclusions
Across prostate cancer disease states, worsening of fatigue was generally observed in the first 13 weeks of treatment, particularly in trials of asymptomatic or minimally symptomatic patients. While ENZA was associated with increased fatigue in early disease states in some patients, most did not experience significant fatigue deterioration. In more advanced disease states, fatigue scores improved over time vs. PBO.
Clinical trial identification
NCT02677896 (ARCHES), NCT02003924 (PROSPER), NCT01212991 (PREVAIL), NCT00974311 (AFFIRM).
Editorial acknowledgement
Medical writing assistance was provided by Emily Ruzich, PhD, from IQVIA. Editorial assistance was provided by Lianne Young, BSc (Hons), and Jane Beck from Complete HealthVizion, funded by the study sponsors.
Legal entity responsible for the study
Astellas Pharma Inc. and Pfizer Inc.
Funding
This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide.
Disclosure
B.F. Tombal: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas ; Honoraria (self): Bayer; Honoraria (self): Janssen; Honoraria (self): Sanofi; Advisory/Consultancy: Amgen; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Takeda. S.J. Freedland: Full/Part-time employment, Spouse/Financial dependant: Genomic Health; Full/Part-time employment, Spouse/Financial dependant: Exosome Diagnostics; Advisory/Consultancy: Astellas Pharma Inc. ; Advisory/Consultancy: Janssen Biotech; Advisory/Consultancy: Dendreon; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Ferring; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Sanofi; Research grant/Funding (self), Research grant/Funding (institution): Myriad Genetics; Research grant/Funding (self), Research grant/Funding (institution): Decipher Biosciences; Research grant/Funding (self), Research grant/Funding (institution): Progenika; Research grant/Funding (self), Research grant/Funding (institution): MDx Health; Research grant/Funding (self), Research grant/Funding (institution): OPKO Diagnostics; Research grant/Funding (self), Research grant/Funding (institution): Diasorin. A.J. Armstrong: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Dendreon; Advisory/Consultancy, Research grant/Funding (institution): Medivation; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen Biotech; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Scientific and Medical Affairs Inc; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: AstraZeneca; Licensing/Royalties: Circulating tumor cell novel capture technology; Honoraria (self), Research grant/Funding (institution): Janssen Oncology; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Gilead Sciences; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Active Biotech; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Constellation Pharmaceuticals; Research grant/Funding (institution): Merck. T.M. Beer: Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Janssen Biotech; Advisory/Consultancy: Janssen Japan; Advisory/Consultancy: Merck; Research grant/Funding (institution): Corcept Therapeutics; Research grant/Funding (institution): Janssen Research & Development; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): OncoGenex; Research grant/Funding (institution): Sotio; Advisory/Consultancy: Pfizer. A. Stenzl: Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: Alere; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Steba Biotech; Travel/Accommodation/Expenses: Sanofi/Aventis; Travel/Accommodation/Expenses: CureVac; Travel/Accommodation/Expenses: Ferring; Speaker Bureau/Expert testimony: GBA; Licensing/Royalties: Patent A290/99 Implantable incontinence device; Licensing/Royalties: AT00/0001:C-Trap, implantable device to treat urinary incontinence; Licensing/Royalties: 2018/6579 Gene-expression signature for subtype and prognostic prediction of renal cell carcinoma; Research grant/Funding (self): Karl Storz; Research grant/Funding (self): Astellas Pharma; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Medivation. C.N. Sternberg: Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Astellas; Advisory/Consultancy: Sanofi-Genzyme; Advisory/Consultancy: Roche-Genentech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Medscape; Advisory/Consultancy: UroToday. M. Hussain: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Lecture fees: Astellas Pharma; Speaker Bureau/Expert testimony, Lecture fees: Physicians' Education Resource; Speaker Bureau/Expert testimony, Lecture fees: Sanofi/Genzyme; Speaker Bureau/Expert testimony, Lecture fees: Phillips Gilmore Oncology; Speaker Bureau/Expert testimony, Lecture fees: Medical Learning Institute PeerView; Speaker Bureau/Expert testimony, Fees for educational materials: Projects in Knowledge; Speaker Bureau/Expert testimony, Fees for educational interview: Research in Practice; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self): Daiichi Sankyo Company. A. Ganguli: Full/Part-time employment: Astellas Pharma Global Development. K. Ramaswamy: Full/Part-time employment: Pfizer Inc. H.S. Bhadauria: Full/Part-time employment: Astellas Pharma Global Development. C. Ivanescu: Research grant/Funding (institution), I am an employee of IQVIA which received funding from Astellas to conduct the statistical analyses for this work under consultancy contract: Astellas. J. Turnbull: Research grant/Funding (institution), I am an employee of IQVIA which received funding from Astellas to conduct the statistical analyses for this work under consultancy contract: Astellas. S. Holmstrom: Full/Part-time employment: Astellas Pharma Inc. Leiden. F. Saad: Advisory/Consultancy, Research grant/Funding (self): Astellas ; Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy, Research grant/Funding (self): Sanofi; Advisory/Consultancy, Research grant/Funding (self): Bayer.