New analyses published in The Lancet Oncology showed that enzalutamide (Xtandi®) improves overall quality of life (QoL) in elderly patients with metastatic castration-resistant prostate cancer (mCRPC) in addition to improving overall survival.
Specifically, patients treated with enzalutamide had prolonged time to first skeletal-related event (SRE), pain progression, and health-related QoL (HRQoL) deterioration compared with those in the placebo group. In addition, those receiving enzalutamide reported greater overall improvement in HRQoL, including pain severity and physical, social, emotional, and functional well-being.1
In the phase 3, double-blind AFFIRM trial, 800 patients with mCRPC were treated with 160 mg of enzalutamide orally each day while 399 patients took a placebo. Researchers found that the median time to the first SRE was 16.7 months (95% CI, 14.6 to 19.1) in the enzalutamide group and 13.3 months (95% CI, 9.9 to not yet reached) in the placebo group (hazard ratio 0.69 [95% CI, 0.57 to 0.84] P=0.0001).
Of the 625 evaluable patients taking enzalutamide, 28% reported pain progression at week 13 compared with 39% of 259 patients who received placebo (difference -11.2% [95% CI, -18.1 to -4.3] P=0.0018) with a median time to pain progression not yet reached in the treatment group versus 13.8 months in the placebo group (hazard ratio 0.56 [95% CI, 0.41 to 0.78] P=0.0004). There was a -0.65 difference (95% CI, -0.89 to -0.41; P<0.0001) in the mean pain score, based on the Brief Pain Inventory-Short Form, in the enzalutamide group compared with the placebo group.
Furthermore, 42% of 652 evaluable patients treated with enzalutamide reported overall improvement in HRQoL versus 15% of 248 patients receiving placebo (P<0.0001) with a median time to HRQoL deterioration of 9.0 months (95% CI, 8.3 to 11.1; P<0.0001) versus 3.7 months (95% CI, 3.0 to 4.2; P<0.0001), respectively.1
Enzalutamide, initially approved by the U.S. Food and Drug Administration (FDA) in 2012, is an oral androgen receptor antagonist indicated for the treatment of patients with mCRPC who have previously received docetaxel.2 The AFFIRM trial primary endpoint results published in the New England Journal of Medicine in 2012, which resulted in FDA approval, demonstrated a significantly improved overall survival in those receiving enzalutamide compared with placebo (18.4 months vs 13.6 months; P<0.001).3
Patients treated for prostate cancer often report declines in their QoL, typically during androgen deprivation therapy (ADT), one of the most common treatment methods for patients with advanced prostate cancer.4 ADT can include surgical castration, treatment with luteinizing hormone-releasing (LHRH) analogs, LHRH antagonists, and/or anti-androgens.5
Men starting ADT often report unwanted changes in various HRQoL areas, most likely due to the numerous adverse events associated with ADT, including sexual dysfunction, vasomotor flushing, fatigue, anemia, gynecomastia, osteoporosis, and metabolic complications.4
Because enzalutamide is only indicated for the treatment of patients with mCRPC who have previously been treated with docetaxel, and therefore most likely have undergone ADT prior to and in conjunction with docetaxel and enzalutamide, patients have already experienced the adverse effects caused by ADT.
During the AFFIRM study, all patients had castrate levels of testosterone, but the enzalutamide group had a higher incidence of hot flashes, fatigue, and diarrhea.1 Because all patients were ADT-experienced, their HRQoL would be expected to improve on enzalutamide due to decreased tumor burden despite increases in typical ADT adverse events that they have been exposed to previously.
- Fizazi K, Scher HI, Miller K, et al. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomized, phase 3 AFFIRM trial. Lancet Oncol. 2014 Aug 4. doi: 10.1016/S1470-2045(14)70303-1. [Epub ahead of print]
- Xtandi [package insert]. Northbrook, IL: Astella Pharma US, Inc. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203415lbl.pdf
- Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187-1197.
- Admadi H, Daneshmand S. Androgen deprivation therapy for prostate cancer: long-term safety and patient outcomes. Patient Relat Outcome Meas. 2014;5:63-70.
- NCCN Clinical Practice Guidelines in Oncology™. Prostate Cancer. v 2.2014. Accessed April 6, 2014.