Impact of enzalutamide on quality of life in men with metastatic castration-resistant prostate cancer after chemotherapy: additional analyses from the AFFIRM randomized clinical trial

Abstract

Background: To present longitudinal changes in Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores during 25-week treatment with enzalutamide or placebo in men with progressive metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy in the AFFIRM trial.

Patients and methods: Patients were randomly assigned to enzalutamide 160 mg/day or placebo. FACT-P was completed before randomization, at weeks 13, 17, 21, and 25, and every 12 weeks thereafter while on study treatment. Longitudinal changes in FACT-P scores from baseline to 25 weeks were analyzed using a mixed effects model for repeated measures (MMRM), with a pattern mixture model (PMM) applied as secondary analysis to address non-ignorable missing data. Cumulative distribution function (CDF) plots were generated and different methodological approaches and models for handling missing data were applied. Due to the exploratory nature of the analyses, adjustments for multiple comparisons were not made. AFFIRM is registered with ClinicalTrials.gov, number NCT00974311.

Results: The intention-to-treat FACT-P population included 938 patients (enzalutamide, n = 674; placebo n = 264) with evaluable FACT-P assessments at baseline and ≥1 post-baseline assessment. After 25 weeks, the mean FACT-P total score decreased by 1.52 points with enzalutamide compared with 13.73 points with placebo (P < 0.001). In addition, significant treatment differences at week 25 favoring enzalutamide were evident for all FACT-P subscales and indices, whether analyzed by MMRM or PMM. CDF plots revealed differences favoring enzalutamide compared with placebo across the full range of possible response levels for FACT-P total and all disease- and symptom-specific subscales/indices.

Conclusion: In men with progressive mCRPC after docetaxel-based chemotherapy, enzalutamide is superior to placebo in health-related quality-of-life outcomes, regardless of analysis model or threshold selected for meaningful response.

Clinical trial number: NCT00974311.

Keywords: health-related quality of life; metastatic castration-resistant prostate cancer; patient-reported outcomes.

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Figures

Figure 1.

Adjusted mean changes from baseline for enzalutamide and placebo analyzed using MMRM and PMM with placebo-based pattern imputation (ITT FACT-P population). The shaded band on each graph represents the range of likely important differences for each score (see methods for details). ΔMMRM, adjusted mean change from baseline with enzalutamide versus placebo at week 25, MMRM analysis; ΔPMM, adjusted mean change from baseline with enzalutamide versus placebo at week 25, PMM analysis; *P < 0.001, †P < 0.05. FACT-G, Functional Assessment of Cancer Therapy-General; FACT-P, Functional Assessment of Cancer Therapy-Prostate; FAPSI, FACT Advanced Prostate Symptom Index; ITT, intention-to-treat; MMRM, mixed model repeated measures; PCS, prostate cancer subscale; PMM, pattern mixture model.

Figure 2.

CDF of percent changes of FACT-P scores from baseline for enzalutamide and placebo at each visit (ITT FACT-P population). Note: a positive change indicates improvement. CDF, cumulative distribution function; ITT, intention-to-treat; FACT-G, Functional Assessment of Cancer Therapy-General; FACT-P, Functional Assessment of Cancer Therapy-Prostate; FAPSI, FACT Advanced Prostate Symptom Index.