Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP

Abstract

PURPOSE We previously reported that enzalutamide improved overall survival when added to standard of care in metastatic, hormone-sensitive prostate cancer. Here, we report its effects on aspects of health-related quality of life (HRQL). METHODS HRQL was assessed with the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire and QLM-PR25 at weeks 0, 4, 12, and then every 12 weeks until progression. Scores from week 4 to 156 were analyzed with repeated measures modeling to calculate group means and differences. Deterioration-free survival was from random assignment until the earliest of death, clinical progression, discontinuation of study treatment, or a worsening of 10 points or more from baseline in fatigue, physical function, cognitive function, or overall health and quality of life (OHQL). HRQL scores range from 0 (lowest possible) to 100 (highest possible). RESULTS HRQL was assessed in 1,042 of 1,125 participants (93%). Differences in means favored control over enzalutamide for fatigue (5.2, 95% CI, 3.6 to 6.9; P < .001), cognitive function (4.0, 95% CI, 2.5 to 5.5; P < .001), and physical function (2.6, 95% CI, 1.3 to 3.9; P < .001), but not OHQL (1.2, 95% CI, −0.2 to 2.7; P = .1). Deterioration-free survival rates at 3 years, and log-rank P values comparing the whole distributions, favored enzalutamide over control for OHQL (31% v 17%; P < .0001), cognitive function (31% v 20%; P = .001), and physical function (31% v 22%; P < .001), but not fatigue (24% v 18%; P = .16). The effects of enzalutamide on HRQL were independent of baseline characteristics. CONCLUSION Enzalutamide was associated with worsening of self-reported fatigue, cognitive function, and physical function, but not OHQL. Enzalutamide was associated with improved deterioration-free survival for OHQL, physical function, and cognitive function because delays in disease progression outweighed early deteriorations in these aspects of HRQL.

Reply to L. Marandino et al

“…For example, Figure 2A of our report 3 shows that 10point or greater deteriorations in self-rated cognitive function within 3 months were more frequent among participants assigned enzalutamide than control (39% v 30%; difference 9%; 95% CI, 3 to 15). We also reported these frequencies within subgroups (Fig 2B) in which testosterone suppression was used without docetaxel or enzalutamide (27%) or in combination with docetaxel alone (34%), with enzalutamide alone (35%), or with both enzalutamide and docetaxel (44%).…”

Combination therapy in metastatic hormone-sensitive prostate cancer: is three a crowd?

“…Initial minor adverse effects on health-related quality-of-life measures did not persist, and ultimately were outweighed by the benefits of treatment. 34 …”

“… 40 TITAN, ARCHES, and ENZAMET showed either improvement with apalutamide or enzalutamide, or no clinically relevant differences from control, in several PROM measures. 34 Early decreases in various quality of life domains in ENZAMET may in part be attributable to concurrent docetaxel. 34 The comparison of abiraterone and docetaxel in STAMPEDE showed a clinically meaningful improvement in global quality-of-life scores favouring abiraterone in the first year of treatment.…”

“… 34 Early decreases in various quality of life domains in ENZAMET may in part be attributable to concurrent docetaxel. 34 The comparison of abiraterone and docetaxel in STAMPEDE showed a clinically meaningful improvement in global quality-of-life scores favouring abiraterone in the first year of treatment. 41 …”

Reply to L. Marandino et al

“…We had the opportunity to discuss the measurement of quality-of-life (QOL) outcomes in prostate cancer clinical trials in the context of the recently published study by Stockler et al 1 in which they characterized the QOL outcomes from ENZAMET, an international phase III trial of enzalutamide versus active control (physician's choice of bicalutamide, nilutamide, or flutamide) in combination with androgen deprivation therapy (ADT) in metastatic hormone–sensitive prostate cancer. 2 In response to this publication, Marandino et al 3 raised important points regarding the importance of cognitive function as a crucial QOL outcome requiring accurate and uniform measurement in patients with prostate cancer receiving novel hormonal therapy (NHT) such as enzalutamide in combination with ADT.…”