abiraterone-acetate and Pain

Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patient-reported pain and functional status in a preplanned interim analysis of a phase 3 trial.. Between April 28, 2009, and June 23, 2010, patients with progressive, metastatic castration-resistant prostate cancer were enrolled into a multinational, double-blind, placebo-controlled trial. Patients were eligible if they were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form [BPI-SF] questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy. Patients were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Pain was assessed with the BPI-SF questionnaire, and health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. We analysed data with prespecified criteria for clinically meaningful pain progression and deterioration in HRQoL. All patients who underwent randomisation were included in analyses.. 1088 patients underwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus prednisone. At the time of the second prespecified interim analysis, median follow-up was 22·2 months (IQR 20·2-24·8). Median time to progression of mean pain intensity was longer in patients assigned to abiraterone plus prednisone (26·7 months [95% CI 19·3-not estimable]) than in those assigned to placebo plus prednisone (18·4 months [14·9-not estimable]; hazard ratio [HR] 0·82, 95% CI 0·67-1·00; p=0·0490), as was median time to progression of pain interference with daily activities (10·3 months [95% CI 9·3-13·0] vs 7·4 months [6·4-8·6]; HR 0·79, 95% CI 0·67-0·93; p=0·005). Median time to progression of worst pain was also longer with abiraterone plus prednisone (26·7 months [95% CI 19·4-not estimable]) than with placebo plus prednisone (19·4 months [16·6-not estimable]), but the difference was not significant (HR 0·85, 95% CI 0·69-1·04; p=0·109). Median time to HRQoL deterioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to placebo plus prednisone as assessed by the FACT-P total score (12·7 months [95% CI 11·1-14·0] vs 8·3 months [7·4-10·6]; HR 0·78, 95% CI 0·66-0·92; p=0·003) and by the score on its prostate-cancer-specific subscale (11·1 months [8·6-13·8] vs 5·8 months [5·5-8·3]; HR 0·70, 95% CI 0·60-0·83; p<0·0001).. Abiraterone plus prednisone delays patient-reported pain progression and HRQoL deterioration in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. These results provide further support for the efficacy of abiraterone in this population.

Topics: Abiraterone Acetate; Activities of Daily Living; Androstadienes; Antineoplastic Combined Chemotherapy Protocols; Australia; Canada; Cost of Illness; Disease Progression; Double-Blind Method; Drug Administration Schedule; Europe; Humans; Kaplan-Meier Estimate; Male; Pain; Pain Measurement; Prednisone; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Surveys and Questionnaires; Time Factors; Treatment Outcome; United States

In the COU-AA-302 study (NCT00887198), abiraterone acetate plus prednisone (AAP) significantly improved outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) versus prednisone alone. Baseline clinical parameters predicting that treatment response could help inform clinical decisions were explored.. To identify patients who derive the greatest clinical benefit from AAP treatment.. A total of 1088 mCRPC patients treated with either AAP or prednisone in the first-line setting in COU-AA-302 were included in this post hoc analysis.. Abiraterone acetate1000mg daily versus placebo, both plus prednisone 10mg daily.. Univariate and multivariable Cox regression analyses were performed, including clinical and pathological parameters for the primary end points overall survival (OS) and radiographic progression-free survival (rPFS), and secondary study end points. Tumor-associated baseline parameters independently impacting OS were applied to stratify patients according to possible treatment effects.. Baseline prostate-specific antigen (PSA), tumor-related pain as assessed by the Brief Pain Inventory-Short Form (BPI-SF), and Gleason score (GS) at primary diagnosis were identified as tumor-associated variables that independently impacted OS. AAP significantly improved outcomes versus prednisone in both group 1 (BPI-SF 0-1 and PSA <80 ng/ml and GS <8; p=0.006; hazard ratio [HR]: 0.61) and group 2 (BPI-SF 2-3 and/or PSA ≥80 ng/ml and/or GS ≥8; p=0.03; HR: 0.84). The differences observed for treatment effects between groups 1 and 2 for OS (HR: 0.61 vs 0.84), rPFS (HR: 0.41 vs 0.59), and time to chemotherapy (HR: 0.64 vs 0.71) were not statistically significant.. AAP significantly improved outcomes in mCRPC patients compared with prednisone alone regardless of baseline pain and PSA level, and GS at primary diagnosis with no significant differences between observed treatment effects in groups 1 and 2.. Treatment with abiraterone acetate and prednisone (compared with treatment with prednisone only) for metastatic castration-resistant prostate cancer increased survival in all patients in the study regardless of pain, prostate-specific antigen levels at the start of treatment, and Gleason score at primary diagnosis.

Topics: Abiraterone Acetate; Aged; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Humans; Male; Middle Aged; Neoplasm Grading; Pain; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Survival Analysis

Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patient-reported pain and functional status in a preplanned interim analysis of a phase 3 trial.. Between April 28, 2009, and June 23, 2010, patients with progressive, metastatic castration-resistant prostate cancer were enrolled into a multinational, double-blind, placebo-controlled trial. Patients were eligible if they were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form [BPI-SF] questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy. Patients were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Pain was assessed with the BPI-SF questionnaire, and health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. We analysed data with prespecified criteria for clinically meaningful pain progression and deterioration in HRQoL. All patients who underwent randomisation were included in analyses.. 1088 patients underwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus prednisone. At the time of the second prespecified interim analysis, median follow-up was 22·2 months (IQR 20·2-24·8). Median time to progression of mean pain intensity was longer in patients assigned to abiraterone plus prednisone (26·7 months [95% CI 19·3-not estimable]) than in those assigned to placebo plus prednisone (18·4 months [14·9-not estimable]; hazard ratio [HR] 0·82, 95% CI 0·67-1·00; p=0·0490), as was median time to progression of pain interference with daily activities (10·3 months [95% CI 9·3-13·0] vs 7·4 months [6·4-8·6]; HR 0·79, 95% CI 0·67-0·93; p=0·005). Median time to progression of worst pain was also longer with abiraterone plus prednisone (26·7 months [95% CI 19·4-not estimable]) than with placebo plus prednisone (19·4 months [16·6-not estimable]), but the difference was not significant (HR 0·85, 95% CI 0·69-1·04; p=0·109). Median time to HRQoL deterioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to placebo plus prednisone as assessed by the FACT-P total score (12·7 months [95% CI 11·1-14·0] vs 8·3 months [7·4-10·6]; HR 0·78, 95% CI 0·66-0·92; p=0·003) and by the score on its prostate-cancer-specific subscale (11·1 months [8·6-13·8] vs 5·8 months [5·5-8·3]; HR 0·70, 95% CI 0·60-0·83; p<0·0001).. Abiraterone plus prednisone delays patient-reported pain progression and HRQoL deterioration in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. These results provide further support for the efficacy of abiraterone in this population.

Topics: Abiraterone Acetate; Activities of Daily Living; Androstadienes; Antineoplastic Combined Chemotherapy Protocols; Australia; Canada; Cost of Illness; Disease Progression; Double-Blind Method; Drug Administration Schedule; Europe; Humans; Kaplan-Meier Estimate; Male; Pain; Pain Measurement; Prednisone; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Surveys and Questionnaires; Time Factors; Treatment Outcome; United States

Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months.. We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated.. Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved ≥50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR.. With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.

Topics: Abiraterone Acetate; Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Male; Pain; Prednisone; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Retrospective Studies

To describe the patterns of second-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment in a Spanish population, to identify the factors associated with those patterns, and to compare the efficacy and safety of the treatments most frequently administered.. Observational, prospective study conducted in patients with histologically or cytologically confirmed prostate adenocarcinoma; documented metastatic castration-resistant disease; progression after first-line, docetaxel-based chemotherapy with or without other agents.. Of the 150 patients recruited into the study, 100 patients were prescribed abiraterone acetate plus prednisone (AAP), 44 patients received cabazitaxel plus prednisone (CP), and 6 patients received other treatments. Age (odds ratio [OR] 1.06, 95% [confidence interval] CI 1.01 to 1.11) and not elevated lactate dehydrogenase (LDH) levels (OR 0.33, 95% CI 0.14 to 0.76) were independently associated with the administration of AAP. Treatment with AAP was associated with significantly longer clinical/radiographic progression-free survival (hazard ratio [HR] 0.57, 95% CI 0.38 to 0.85) and overall survival (OS; HR 0.40, 95% CI 0.21 to 0.76) compared to CP, while no significant differences between the treatments were found regarding biochemical progression-free survival (PFS; HR 0.78 [95% CI 0.49 to 1.24]). However, in a post-hoc Cox regression analysis adjusted for potential confounders there were not differences between AAP and CP in any of the time-to-event outcomes, including overall survival. We observed no new safety signals related to either regimen.. Second-line AAP for patients with mCRPC is the most common treatment strategy after progression with a docetaxel-based regimen. When controlling for potential confounders, patients receiving this treatment showed no differences in PFS and OS in comparison to those receiving CP, although these latter results should be confirmed in randomized controlled trials.

Topics: Abiraterone Acetate; Adenocarcinoma; Age Factors; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Docetaxel; Humans; Kaplan-Meier Estimate; L-Lactate Dehydrogenase; Male; Middle Aged; Multivariate Analysis; Pain; Prednisone; Progression-Free Survival; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Spain; Taxoids; Treatment Outcome

Topics: Abiraterone Acetate; Humans; Male; Neoplasm Grading; Pain; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant