Introduction:

The Phase 3 ARCHES trial (NCT02677896) showed that enzalutamide + androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) versus placebo + ADT in men with metastatic hormone-sensitive prostate cancer (mHSPC). Here we report patient-reported outcome (PRO) data with a focus on fatigue up to week 73.

Methods:

PROs, including the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and Brief Pain Inventory–Short Form (BPI-SF), were assessed at baseline, week 13, and every 12 weeks until disease progression. Many patients initiated ADT for several months prestudy baseline (>20% of patients in each group had previously used ADT for >3 months). Most patients (63% overall) had high-volume disease and about 20% of patients with high-volume disease initiated enzalutamide or placebo after docetaxel therapy. Change from baseline was assessed using mean scores and mixed model repeated measures. The proportion of patients scoring 0–4 on indicators of fatigue (FACT-P items GP1 ["I have a lack of energy"] and GP7 ["I am forced to spend time in bed"] were measured over time. The proportion of patients with item scores classified as worsening (by 1, 2, or ≥3 points versus baseline), stable, or improved (by 1, 2, or ≥3 points versus baseline) over time was also measured.

Results:

Completion rates (≥1 scale with nonmissing values) were high (88−96%) for FACT-P and BPI-SF up to week 73. Both groups were generally asymptomatic at baseline, with good health-related quality of life (HRQoL) [mean (SD) FACT-P total score: placebo + ADT 112.7 (19.0); enzalutamide + ADT 113.9 (19.8)] and low pain (worst pain [item 3]: placebo + ADT 1.77 [2.3]; enzalutamide + ADT 1.80 [2.4)]). HRQoL and pain scores remained stable over time, with no clinically meaningful between-group differences in change from baseline to week 73. Enzalutamide + ADT maintained HRQoL, as measured with FACT-P total score across 73 weeks, at the same level as placebo + ADT. For item GP1 at baseline, the proportion of patients with more than a little lack of energy (i.e., somewhat, quite a bit, or very much; item score >1) was similar between groups (35.9% of enzalutamide and 37.0% of placebo patients). At week 73, the proportion of patients with stable (enzalutamide 39.0%; placebo 36.4%) or improved (enzalutamide 41.5%; placebo 32.4%) lack of energy was similar in both groups (Figure 1). For GP7 at baseline, most patients were not forced to spend time in bed and this was similar between groups (76.4% of enzalutamide patients and 79.6% of placebo patients had a score of 0 [not at all]). At week 73, the proportion of patients who were stable (enzalutamide 73.2%; placebo 82.8%) or had improved (enzalutamide 12.1%; placebo 9.1%) regarding being forced to spend time in bed was similar in both groups (Figure 2).

Conclusion:

Men with mHSPC were generally asymptomatic, with high HRQoL and low pain at baseline, likely due to many patients initiating ADT several months prestudy. No clinically meaningful differences in HRQoL were observed between enzalutamide and placebo. Similar proportions of patients in enzalutamide and placebo groups reported stable or improved fatigue item scores at week 73.

Funding: This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide. Medical writing and editorial assistance were provided by Tom Lavelle from Bioscript and Folabomi Oladosu, PhD, and Jane Beck from Complete HealthVizion, funded by the study sponsors.