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Commentary on: Abiraterone in Metastatic Prostate Cancer Without Previous Chemotherapy
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TLDR
Abiraterone inhibits CYP-17, a crucial enzyme in androgen biosynthesis in the testes, adrenal glands, and in prostate cancer cells as discussed by the authors, and showed a strong trend toward improved survival.Abstract:
n this prospective, multicenter, phase 3 trial, 1088 patients with asymptomatic or mildly symptomatic Imetastatic castrate-resistant prostate cancer (mCRPC) were randomized to receive abiraterone (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. Abiraterone inhibits CYP-17, a crucial enzyme in androgen biosynthesis in the testes, adrenal glands, and in prostate cancer cells. The trial was designed with 2 coprimary end points: radiographic progression-free survival and overall survival. This report was based on a planned interim analysis after 43% (333 of 773) of expected deaths had occurred. The findings were significant enough to warrant unblinding so that patients in the placebo arm could be offered abiraterone. The progression-free survival improved from 8.3 months to 16.5 months with abiraterone (hazard ratio, 0.53; 95% confidence interval, 0.45-0.62; P <.001). The median overall survival was not reached in the abiraterone group but was 27.2 months in the control arm (hazard ratio, 0.75; 95% confidence interval, 0.61-0.93; P 1⁄4 .0097). This did not reach the prespecified P value of .0008 to achieve statistical significance, so that at the time of this interim analysis, it can only be concluded that abiraterone showed a strong trend toward improved survival. Further benefits were observed in secondary end points, including time to initiation of cytotoxic chemotherapy (25.2 vs 16.8 months), to opiate use for cancer-related pain (not reached vs 23.7 months), to prostate-specific antigen progression (11.1 vs 5.6 months), and to a 1-point decline in Eastern Cooperative Oncology Group performance status (12.3 vs 10.9 months). These important milestones in the course of mCRPC were all delayed. Toxicity related to abiraterone was observed, but because prednisone was administered in both treatment groups, rates of toxicity in the control arm were not much different. Grade 3 or 4 adverse events were reported by 48% of patients in the abiraterone arm and by 42% of patients in the control arm. Fatigue, arthralgia, and peripheral edema were important adverse effects observed more frequently in the abiraterone arm. Other signs ofread more
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Efficacy and safety of abiraterone acetate plus prednisone in Japanese patients with newly diagnosed, metastatic hormone-naive prostate cancer: final subgroup analysis of LATITUDE, a randomized, double-blind, placebo-controlled, phase 3 study
Hiroyoshi Suzuki,Toshitaka Shin,Satoshi Fukasawa,Katsuyoshi Hashine,Sumiko Kitani,Noriyuki Ohtake,Kazuhiro Shibayama,Namphuong Tran,Suneel Mundle,Karim Fizazi,Nobuaki Matsubara +10 more
TL;DR: Overall survival and safety results from the final analysis of the Japanese subgroup of the LATITUDE study are presented, showing favorable efficacy and safety outcomes in patients with newly diagnosed, high-risk metastatic hormone-naïve prostate cancer.
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A Phase I/II Study of the Investigational Drug Alisertib in Combination With Abiraterone and Prednisone for Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Abiraterone
Jianqing Lin,Jianqing Lin,Sheel A. Patel,Ashwin Reddy Sama,Jean H. Hoffman-Censits,Brooke Kennedy,Deborah Kilpatrick,Zhong Ye,Hushan Yang,Zhaomei Mu,Benjamin E. Leiby,Nancy L. Lewis,Massimo Cristofanilli,William Kevin Kelly +13 more
TL;DR: A tolerable dose of alisertib in combination with AP in mCRPC was not established in this study, and the trial was terminated early.
Journal ArticleDOI
Impact on abiraterone pharmacokinetics and safety: Open-label drug-drug interaction studies with ketoconazole and rifampicin.
Apexa Bernard,Nicole Vaccaro,Milin Acharya,James Jiao,Johan Monbaliu,Ronald de Vries,Hans Stieltjes,Margaret K. Yu,Namphuong Tran,Caly Chien +9 more
TL;DR: Strong CYP3A4 inducers should be avoided or used with careful evaluation of clinical efficacy when administered with abiraterone acetate.
Journal ArticleDOI
Neoadjuvant therapy for localized prostate cancer: Examining mechanism of action and efficacy within the tumor.
David Y. Lou,Lawrence Fong +1 more
TL;DR: The use of neoadjuvant androgen-deprivation therapy and chemotherapy either singly or in combination before radical prostatectomy is generally safe and feasible while reducing prostate volume and tumor burden and preoperative therapy is not the current standard of care in prostate cancer treatment.
Journal Article
Resistance to abiraterone in castration-resistant prostate cancer: A review of the literature
Silvana Giacinti,Maria Bassanelli,Anna Maria Aschelter,Annalisa Milano,Michela Roberto,Paolo Marchetti +5 more
TL;DR: The aim of the present review is to describe the main data currently available on resistance to abiraterone, a CYP17A1 inhibitor, and its role in castration-resistant prostate cancer.
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