Effect of abiraterone acetate on fatigue in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy.

BACKGROUND: Fatigue is a common, debilitating side-effect of prostate cancer and its treatment. Patient-reported fatigue was evaluated as part of COU-AA-301, a randomized, placebo-controlled, phase III trial of abiraterone acetate and prednisone versus placebo and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients after docetaxel chemotherapy. This is the first phase III study in advanced prostate cancer to evaluate fatigue outcomes using a validated fatigue-specific instrument. PATIENTS AND METHODS: The Brief Fatigue Inventory (BFI) questionnaire was used to measure patient-reported fatigue intensity and fatigue interference with activities of daily life. All analyses were conducted using prespecified responder definitions of clinically meaningful changes. RESULTS: A total of 797 patients were randomized to abiraterone acetate and prednisone, and 398 were randomized to placebo and prednisone. Compared with prednisone alone, in patients with clinically significant fatigue at baseline, abiraterone acetate and prednisone significantly increased the proportion of patients reporting improvement in fatigue intensity (58.1% versus 40.3%, P = 0.0001), improved fatigue interference (55.0% versus 38.0%, P = 0.0075), and accelerated improvement in fatigue intensity (median 59 days versus 194 days, P = 0.0155). CONCLUSIONS: In patients with mCRPC progressing after docetaxel chemotherapy, abiraterone acetate and prednisone yielded clinically meaningful improvements in patient-reported fatigue compared with prednisone alone.

Evaluation of quality of life in a clinical trial with nonrandom dropout: the effect of epoetin alfa in anemic cancer patients.

Quality of life (QOL) endpoints from a randomized, placebo-controlled trial of anemic cancer patients treated with nonplatinum-containing chemotherapy who received epoetin alfa or placebo were subjected to a sensitivity analysis. Three QOL instruments were used: the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Cancer Linear Analog Scale (CLAS), and the Medical Outcomes Study Short Form-36 (SF-36). The seven primary endpoints chosen a priori for analysis were: the Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-An fatigue subscale, CLAS energy, CLAS daily activities, CLAS overall QOL, and the SF-36 physical and mental component summary scales. Lower QOL scores were reported for patients who discontinued early, suggesting a nonrandom dropout process. Significant correlations (ranging from 0.37 to 0.77) between individual rates of change and the time to early termination of therapy or death supported this conclusion. Estimates of within-treatment-arm QOL change over time are more conservative with the missing not at random (MNAR) assumption as compared with the more optimistic estimates with the assumption that missing QOL data are missing at random (MAR). However, the between-treatment-arm comparisons were consistent across analyses, demonstrating statistically significant differences in favor of the epoetin alfa arm for four of the seven outcome measures.

Assessing the clinical significance of health-related quality of life (HrQOL) improvements in anaemic cancer patients receiving epoetin alfa.

Health-related quality of life (HrQOL) assessments are gaining importance as outcome measures in cancer clinical trials. A recently published clinical trial reported statistically significant (P<0.001) increases in haemoglobin (Hb) levels and significantly (P<0.01) increased HrQOL scores following the administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) versus placebo to anaemic cancer patients who received non-platinum chemotherapy. This study employed five cancer-specific HrQOL instruments. Hb and HrQOL data from this trial were analysed to estimate the minimally important difference (MID) in HrQOL measures that could be interpreted as clinically meaningful, with Hb level selected as the best external standard. Patients were assigned to two groups: improved (Hb increases of >/=1 g/dL) or stable (change in Hb of-1 g/dL to <1 g/dL). The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group. By this analysis, the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinically important for all Hb-sensitive, cancer-specific HrQOL evaluations. Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinically significant. These analyses were repeated using a data set from a separate clinical trial, which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre, double-blind study were clinically important. These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials.