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      Effect of Baseline Characteristics on Cabazitaxel Treatment Duration in Patients with Metastatic Castration-Resistant Prostate Cancer: A Post Hoc Analysis of the Compassionate Use/Expanded Access Programs and CAPRISTANA Registry

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          Abstract

          We examined factors that may impact cabazitaxel treatment duration in a real-life setting in a compassionate use program, expanded access program, and prospective observational study in metastatic castration-resistant prostate cancer (mCRPC). Patients with mCRPC previously treated with docetaxel (N = 1621) received cabazitaxel 25 mg/m 2 intravenously every 3 weeks until disease progression, death, unacceptable toxicity or physician/patient decision. The median number of cabazitaxel cycles was six (range, 1–49); 708 patients (43.7%) received >6 cycles. Patients receiving >6 cycles tended to have a better Eastern Cooperative Oncology Group performance status of 0–1 ( p = 0.0017 for ≤6 vs. >6 cycles). Overall, 348 patients (21.5%) were ≥75 years of age; 139 (39.9%) received >6 cycles. The main reason for discontinuation was disease progression; however, in patients receiving 1–2 cycles, the main reason for discontinuation was adverse events. Only 52 patients (3.2%) progressed during cycles 1–2. Cabazitaxel was well tolerated in these studies, which included some elderly and frail patients, offering clinicians an important treatment option in the management of mCRPC. Proactive management of adverse events may allow patients to receive a higher number of cabazitaxel cycles and derive greater benefit.

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          Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study.

          Abiraterone acetate improved overall survival in metastatic castration-resistant prostate cancer at a preplanned interim analysis of the COU-AA-301 double-blind, placebo-controlled phase 3 study. Here, we present the final analysis of the study before crossover from placebo to abiraterone acetate (after 775 of the prespecified 797 death events). Between May 8, 2008, and July 28, 2009, this study enrolled 1195 patients at 147 sites in 13 countries. Patients were eligible if they had metastatic castration-resistant prostate cancer progressing after docetaxel. Patients were stratified according to baseline Eastern Cooperative Oncology Group (ECOG) performance status, worst pain over the past 24 h on the Brief Pain Inventory-Short Form, number of previous chemotherapy regimens, and type of progression. Patients were randomly assigned (ratio 2:1) to receive either abiraterone acetate (1000 mg, once daily and orally) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone with a permuted block method via an interactive web response system. The primary endpoint was overall survival, analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00091442. Of the 1195 eligible patients, 797 were randomly assigned to receive abiraterone acetate plus prednisone (abiraterone group) and 398 to receive placebo plus prednisone (placebo group). At median follow-up of 20·2 months (IQR 18·4-22·1), median overall survival for the abiraterone group was longer than in the placebo group (15·8 months [95% CI 14·8-17·0] vs 11·2 months [10·4-13·1]; hazard ratio [HR] 0·74, 95% CI 0·64-0·86; p<0·0001). Median time to PSA progression (8·5 months, 95% CI 8·3-11·1, in the abiraterone group vs 6·6 months, 5·6-8·3, in the placebo group; HR 0·63, 0·52-0·78; p<0·0001), median radiologic progression-free survival (5·6 months, 5·6-6·5, vs 3·6 months, 2·9-5·5; HR 0·66, 0·58-0·76; p<0·0001), and proportion of patients who had a PSA response (235 [29·5%] of 797 patients vs 22 [5·5%] of 398; p<0·0001) were all improved in the abiraterone group compared with the placebo group. The most common grade 3-4 adverse events were fatigue (72 [9%] of 791 patients in the abiraterone group vs 41 [10%] of 394 in the placebo group), anaemia (62 [8%] vs 32 [8%]), back pain (56 [7%] vs 40 [10%]), and bone pain (51 [6%] vs 31 [8%]). This final analysis confirms that abiraterone acetate significantly prolongs overall survival in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment. No new safety signals were identified with increased follow-up. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion.

            Androgen deprivation therapy remains a critical component of treatment for men with advanced prostate cancer, and data support its use in metastatic disease and in conjunction with surgery or radiation in specific settings. Alternatives to standard androgen deprivation therapy, such as intermittent androgen suppression and estrogen therapy, hold the potential to improve toxicity profiles while maintaining clinical benefit. Current androgen deprivation strategies seem to incompletely suppress androgen levels and androgen-receptor-mediated effects at the tissue level. Advances in the understanding of mechanisms that contribute to castration-resistant prostate cancer are leading to rationally designed therapies targeting androgen metabolism and the androgen receptor. The results of large trials investigating the optimization of primary androgen deprivation therapy, including evaluation of intermittent androgen suppression and phase III studies of novel androgen synthesis inhibitors, such as abiraterone acetate, are eagerly awaited.
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              Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer—PROSELICA

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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                17 April 2020
                April 2020
                : 12
                : 4
                : 995
                Affiliations
                [1 ]Clinical Oncology, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral CH63 4JY, UK
                [2 ]Department of Medicine and Health Sciences ‘Vincenzo Tiberio’, University of Molise, 86100 Campobasso, Italy
                [3 ]Medical Oncology, Tortora Hospital, 84016 Pagani, Salerno, Italy
                [4 ]Department of Hematology and Oncology, Regional Hospital Hochsteiermark, 8700 Leoben, Austria
                [5 ]Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
                [6 ]Department of Biostatistics, Sanofi, 91380 Chilly-Mazarin, France
                [7 ]Medical Evidence Generation, Sanofi, 75008 Paris, France
                [8 ]Global Medical Affairs Oncology, Sanofi, Cambridge, MA 02142, USA
                [9 ]Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain
                Author notes
                [* ]Correspondence: zaf.malik@ 123456nhs.net
                [†]

                These authors contribute equally to this study.

                Author information
                https://orcid.org/0000-0001-7520-2908
                Article
                cancers-12-00995
                10.3390/cancers12040995
                7226228
                32316580
                affc9086-67f0-43f4-bb9d-401e9e9286dd
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 February 2020
                : 15 April 2020
                Categories
                Article

                mcrpc,cabazitaxel,real-world,cup,eap,capristana
                mcrpc, cabazitaxel, real-world, cup, eap, capristana

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