medwireNews: The addition of enzalutamide rather than a standard nonsteroidal anti-androgen (NSAA) to testosterone suppression is associated with worsening of some health-related quality of life (HRQoL) function and symptom scores in men with metastatic hormone-sensitive prostate cancer (HSPC), report the ENZAMET researchers.
They point out, however, that “[t]hese impairments did not worsen over time, and better disease control improved deterioration-free survival rates at 3 years because the modest detrimental effects on aspects of [HRQoL] were outweighed by subsequent delays in disease progression.”
The phase 3 trial previously showed that the use of enzalutamide 160 mg/day versus a standard NSAA (bicalutamide, nilutamide, or flutamide) alongside testosterone suppression improved overall survival and delayed progression. The current report, published in the Journal of Clinical Oncology, focuses on the prespecified secondary endpoint of HRQoL, which was evaluated in 1042 of the 1125 trial participants.
Over 3 years of follow-up, the mean overall HRQoL score did not differ significantly between the enzalutamide and control groups, but there were statistically significant mean between-group differences favoring the latter for physical (2.6 points), role (3.6 points), social (3.3 points), and cognitive (4.0 points) functioning.
Similarly, the differences in means significantly favored the control regimen for fatigue (5.2 points), appetite loss (2.5 points), and urinary symptoms (1.9 points), with a trend toward worsening for dyspnea (1.8 points).
However, the “[d]ifferences between the randomly assigned treatment groups, and their upper 95% confidence limits, were below our prespecified threshold for a minimum clinically important difference of 10 points,” note the researchers.
They also report on deterioration-free survival, “a novel measure of net benefit” defined as the time from randomization until the earliest of death, clinical progression, discontinuation, or a worsening of at least 10 points in the pertinent HRQoL domain without a subsequent comparably sized improvement.
The Kaplan–Meier curves for this endpoint favored the control arm over the enzalutamide arm for physical function, cognitive function, and fatigue during the first 3 months, “mainly attributable to early deteriorations in HRQL because of treatment,” say Martin Stockler (University of Sydney, New South Wales, Australia) and co-investigators.
But the curves crossed at around the 6-month mark, and the 3-year deterioration-free survival rates significantly favored enzalutamide over control for overall HRQoL (31 vs 17%), physical functioning (31 vs 22%), and cognitive functioning (31 vs 20%), but not fatigue (24 vs 18%).
The researchers note that around 45% of patients in the trial were given planned early docetaxel and subgroup analysis confirmed that receipt of this chemotherapy did not significantly modify the impact of enzalutamide on HRQoL or on deterioration-free survival.
“These analyses indicate that the effects of enzalutamide and planned early docetaxel on [HRQoL] were independent, incremental, and approximately additive,” they comment.
The team concludes: “Longer follow-up will reveal the effects of enzalutamide beyond 3 years.”
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