Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial

University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: .
The Lancet Oncology (Impact Factor: 24.73). 11/2012; 13(12). DOI: 10.1016/S1470-2045(12)70473-4
Source: PubMed

ABSTRACT 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 defined response criteria that incorporated analgesic use, clinically meaningful changes in pain intensity and interference with daily living. We measured time to first occurrence of skeletal-related events, which we defined 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 significant baseline pain, whereas all other analyses were done in the overall intention-to-treat population. COU-AA-301 is registered with, number NCT00638690. FINDINGS: Median follow-up was 20·2 months (IQR 18·4-22·1). In patients with clinically significant pain at baseline, abiraterone acetate and prednisone resulted in significantly 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 significantly better with abiraterone acetate and prednisone than with prednisone only. In the overall population, median time to occurrence of first skeletal-related event was significantly 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 offer significant benefits 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.

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Available from: Ethan Basch, Apr 09, 2014
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    • "Eur Urol (2014), j.eururo.2014.02.013 analgesic consumption reported in 12–29% of patients [14] [15]. Since the pain palliation signal and the reductions in narcotic use observed with cabozantinib substantially exceed these previously reported levels, an effect beyond placebo is likely and justifies the design and conduct of a dedicated pain palliation phase 3 trial towards a formal indication [16] [34]. "
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    European Urology 02/2014; DOI:10.1016/j.eururo.2014.02.013 · 12.48 Impact Factor
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    • "However , the median time to first SRE was significantly longer in the AA arm than in the placebo arm (25.0 months vs. 20.3 months; P = 0.0001) [27]. Time to first SRE was not evaluated in the TROPIC trial [18]. "
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    Cancer Treatment Reviews 08/2013; 40(1). DOI:10.1016/j.ctrv.2013.06.008 · 6.47 Impact Factor
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    • "Treatment of CRPC is very difficult and not that satisfactory so far. Docetaxel based chemotherapy is one of the most effective ways of treatments [18] [19] [20], but the overall survival benefit is only 2-3 months compared to conventional methods [21]. "
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