Bertrand Tombal, MD
As reported by Bertrand Tombal, MD, of the Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, and colleagues in The Lancet Oncology, treatment with enzalutamide was associated with clinically meaningful delays in pain progression, symptom worsening, and deterioration in functional status vs placebo in the phase III PROSPER trial in nonmetastatic, castration-resistant prostate cancer (ie, histologically or cytologically confirmed adenocarcinoma of the prostate, no evidence of metastases, and increasing prostate-specific antigen values indicating progressive disease during androgen-deprivation therapy). The trial showed that enzalutamide was associated with a significant improvement in metastasis-free survival.
In the trial, 1,401 patients were randomly assigned to receive enzalutamide (n = 933) or placebo (n = 468). Assessed patient-reported outcomes consisted of pain progression using the Brief Pain Inventory Short Form (BPI-SF) and health-related quality of life using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-PR25), the EuroQoL 5-Dimensions 5-Levels health questionnaire visual analog scale (EQ-VAS), and the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaire. Patients completed questionnaires at baseline, week 17, and every 16 weeks thereafter until treatment discontinuation.
Patient-Reported Outcomes
Changes from baseline to week 97 statistically favored enzalutamide for FACT-P social and family well-being (P = .045) and placebo for EORTC QLQ-PR25 hormonal treatment-related symptoms (P = .0020), but neither of the differences met criteria for being clinically meaningful. No significant differences were observed between groups for changes from baseline to week 97 in any other patient-reported outcome score.
Significant differences in time to deterioration in patient-reported outcome domains included the following:
- Time to clinically meaningful pain progression assessed by BPI-SF pain severity scale was longer with enzalutamide (median = 36.83 months vs not reached, hazard ratio [HR] = 0.75, P = .028).
- Time to clinically meaningful symptom worsening was longer with enzalutamide for EORTC QLQ-PR25 urinary symptoms (36.86 vs 25.86 months, HR = 0.58, P < .0001) and bowel symptoms (33.15 vs 25.89 months, HR = 0.72, P = .0018).
- Time to clinically meaningful deterioration was longer with enzalutamide for health-related quality of life for FACT-P total score (22.11 vs 18.43 months, HR = 0.83, P = .037), emotional well-being (36.73 vs 29.47 months, HR = 0.69, P = .0008), and prostate cancer subscale (18.43 vs 14.69 months, HR = 0.79, P = .0042).
- Time to clinically meaningful deterioration in EORTC QLQ-PR25 hormonal treatment–related symptoms was shorter with enzalutamide (33.15 vs 36.83 months, HR = 1.29, P = .035).
- Time to deterioration of EQ-VAS was longer with enzalutamide (22.11 vs 14.5 months, HR = 0.75, P = .0013).
The investigators concluded, “Patients with nonmetastatic, castration-resistant prostate cancer receiving enzalutamide had longer metastasis-free survival than did those who received placebo, while maintaining low pain levels and prostate cancer symptom burden and high health-related quality of life. Enzalutamide showed a clinical benefit by delaying pain progression, symptom worsening, and decrease in functional status compared with placebo. These findings suggest that enzalutamide is a treatment option that should be discussed with patients presenting with high-risk, nonmetastatic, castration-resistant prostate cancer.”
Tombal et al: Lancet Oncol. February 12, 2019 (early release online). ■
