Patient-reported outcomes for patients with metastatic castration-resistant prostate cancer receiving docetaxel and Atrasentan versus docetaxel and placebo in a randomized phase III clinical trial (SWOG S0421) (original) (raw)
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Cancers
Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biologi...
The Lancet Oncology, 2012
Background Bone metastases are a major cause of morbidity in metastatic castration-resistant prostate cancer. Abiraterone acetate potently disrupts intracrine androgen receptor signalling pathways implicated in the progression of the disease, including bone metastases. We assessed data for pain control and skeletal-related events prospectively collected as part of the randomised, phase 3 COU-AA-301 trial of abiraterone acetate plus prednisone versus placebo plus prednisone in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy. Methods The COU-AA-301 trial enrolled patients with metastatic castration-resistant prostate cancer in whom one or two lines of chemotherapy (one docetaxel based) had been unsuccessful and who had Eastern Cooperative Oncology Group performance statuses of 2 or less. Pain intensity and interference of pain with daily activities were assessed with the Brief Pain Inventory-Short Form questionnaire at baseline, day 15 of cycle 1, and day 1 of each treatment cycle thereafter until discontinuation. We assessed, with prospectively defi ned response criteria that incorporated analgesic use, clinically meaningful changes in pain intensity and interference with daily living. We measured time to fi rst occurrence of skeletal-related events, which we defi ned as pathological fracture, spinal cord compression, palliative radiation to bone, or bone surgery, and regularly assessed them throughout the study. Pain palliation was assessed in patients who had clinically signifi cant baseline pain, whereas all other analyses were done in the overall intention-to-treat population. COU-AA-301 is registered with ClinicalTrials.gov, number NCT00638690. Findings Median follow-up was 20•2 months (IQR 18•4−22•1). In patients with clinically signifi cant pain at baseline, abiraterone acetate and prednisone resulted in signifi cantly more palliation (157 of 349 [45•0%] patients vs 47 of 163 [28•8%]; p=0•0005) and faster palliation (median time to palliation 5•6 months [95% CI 3•7-9•2] vs 13•7 months [5•4-not estimable]; p=0•0018) of pain intensity than did prednisone only. Palliation of pain interference (134 of 223 [60•1%] vs 38 of 100 [38•0%], p=0•0002; median time to palliation of pain interference 1•0 months [95% CI 0•9-1•9] vs 3•7 months [2•7-not estimable], p=0•0004) and median duration of palliation of pain intensity (4•2 months [95% CI 3•0-4•9] vs 2•1 months [1•4-3•7]; p=0•0056) were signifi cantly better with abiraterone acetate and prednisone than with prednisone only. In the overall population, median time to occurrence of fi rst skeletal-related event was signifi cantly longer with abiraterone acetate and prednisone than with prednisone only (25•0 months [95% CI 25•0-not estimable] vs 20•3 months [16•9-not estimable]; p=0•0001). Interpretation In patients with metastatic castration-resistant prostate cancer previously treated with docetaxel, abiraterone acetate and prednisone off er signifi cant benefi ts compared with prednisone alone in terms of pain relief, delayed pain progression, and prevention of skeletal-related events. Funding Janssen Research & Development and Janssen Global Services.
The Lancet Oncology, 2013
Background The endothelin pathway has a role in bone metastases, which are characteristic of advanced prostate cancer. Atrasentan, an endothelin receptor antagonist, has shown activity in prostate cancer. We therefore assessed its eff ect on survival in patients with castration-resistant prostate cancer with bone metastases. Methods In a double-blind phase 3 trial, men with metastatic castration-resistant prostate cancer, stratifi ed for progression type (prostate-specifi c antigen or radiological), baseline pain, extraskeletal metastases, and bisphosphonate use, were randomly assigned in a 1:1 ratio to docetaxel (75 mg/m² every 21 days, intravenously) with atrasentan (10 mg/day, orally) or placebo for up to 12 cycles and treated until disease progression or unacceptable toxicity. Patients who did not progress on treatment were permitted to continue atrasentan or placebo for up to 52 weeks. Coprimary endpoints were progression-free survival (PFS) and overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00134056. Findings 498 patients were randomly assigned to the atrasentan group and 496 to the placebo group. The trial was halted early for futility in April, 2011, after a planned interim analysis. Median PFS was 9•2 months (95% CI 8•5-9•9) in the atrasentan group and 9•1 months (8•4-10•2) in the placebo group (hazard ratio 1•02, 0•89-1•16; p=0•81). Median overall survival was 17•8 months (16•4-19•8) in the atrasentan group versus 17•6 months (16•4-20•1) in the placebo group (1•04, 0•90-1•19; p=0•64). 278 (57%) of 492 patients in the atrasentan group had grade 3 and greater toxicity compared with 294 (60%) of 486 in the placebo group (p=0•22). Three deaths in the atrasentan group and seven in the placebo group were judged to be possibly or probably due to protocol treatment. Interpretation Atrasentan, when added to docetaxel, does not improve overall survival or PFS in men with castrationresistant prostate cancer and bone metastases; therefore, single-agent docetaxel should remain as one of the standard treatments.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015
Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory-Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-predn...
Clinical Genitourinary Cancer, 2019
In castration-resistant prostate cancer (CRPC), several life-prolonging drugs have been registered, but patientreported outcomes in daily practice are scare. In our study, 151 patients with CRPC completed quality of life (QoL) questionnaires. Although the majority received life-prolonging drugs, QoL deteriorated during the course of CRPC. Supportive care should be timely thought of to maintain QoL as long as possible. Background: The purpose of this study was to determine generic, cancer-specific, and prostate cancer-specific health-related quality of life (HRQoL), pain and changes over time in patients with metastatic castration-resistant prostate cancer (mCRPC) in daily practice. Patients and Methods: PRO-CAPRI is an observational, prospective study in 10 hospitals in the Netherlands. Patients with mCRPC completed the EQ-5D, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Brief Pain Inventory-Short Form (BPI-SF) every 3 months and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Prostate Cancer Module (EORTC QLQ-PR25) every 6 months for a maximum of 2 years. Subgroups were identified based on chemotherapy pretreatment. Outcomes were generic, cancer-specific, and prostate cancer-specific HRQoL and self-reported pain. Descriptive statistics were performed including changes over time and minimal important differences (MID) between subgroups. Results: In total, 151 included patients answered 873 questionnaires. The median follow-up from the start of the study was 19.5 months, and 84% were treated with at least 1 life-prolonging agent. Overall, patients were in good clinical condition (Eatern Cooperative Oncology Group performance status 0-1 in 78%) with normal baseline hemoglobin, lactate dehydrogenase, and alkaline phosphatase. At M.C.P.K. and H.M.W. contributed equally to this article.
Clinical Genitourinary Cancer, 2017
The aim of the quality of life in second line mCRPC treatment (SEQOND) study was to prospectively evaluate quality of life (QoL) in patients with metastatic castration-resistant prostate cancer in the second-line setting, where different treatment options do exist. In this nationwide QoL analysis we could show an improvement of QoL in approximately 20% of patients irrespective of second-line regimen chosen by the local investigator. No significant differences in QoL parameters between cabazitaxel or other second-line treatments were found. Background: The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castrationresistant prostate cancer (mCRPC) treated with different regimens after first-line docetaxel, as well as disease progression. Patients and Methods: Patients with mCRPC having received first-line chemotherapy with docetaxel were eligible. Second-line treatment choice was at the discretion of the local investigator. All patients had regular assessments of QoL with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, of fatigue with the Brief Fatigue Inventory, and of pain with the McGill Pain Questionnaire-Short Form. The primary end point was QoL maintenance defined as having a maximum decrease in 2 functional domains of the FACT-P. Results: One hundred thirty-eight patients were included in 36 oncology centers across Switzerland. QoL analysis was available for all patients (59 who received cabazitaxel; 79 who received other therapy [OT] including 75 who received abiraterone). No significant differences for any of the end points were found between groups. A numerically higher number of patients had QoL maintenance with OT (25 of 79 patients, 32%) compared with cabazitaxel (8 of 59 patients, 14%). QoL improvement was found in 20% of patients (12 of 59) who received cabazitaxel and 24% (19 of 79) who received OT. Mean FACT-P score did not change in a clinically relevant manner over time in either group. Pain was present in 70% of patients (96 of 138), and a pain response to treatment was noted in 22% (13 of 59) who received cabazitaxel and 29% (23 of 79) who received OT. A similar but minor improvement of fatigue was noted in both groups. Conclusion: Some degree of QoL decrease was seen in most patients regardless of second-line treatment. No significant differences in QoL parameters between cabazitaxel or other second line treatments were found.