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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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Journal ArticleDOI
Differential side effects profile in patients with mCRPC treated with abiraterone or enzalutamide: a meta-analysis of randomized controlled trials.
Raphael Brandao Moreira,Marcio Debiasi,Edoardo Francini,Pier Vitale Nuzzo,Pier Vitale Nuzzo,Guillermo de Velasco,Fernando C. Maluf,Andre P. Fay,Joaquim Bellmunt,Toni K. Choueiri,Fabio A.B. Schutz +10 more
TL;DR: A meta-analysis of randomized controlled trials for mCRPC patients found that abiraterone was associated with an increased risk of cardiovascular events, while enzalutamide wasassociated with an increase risk of fatigue.
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Association Between Androgen Deprivation Therapy Use and Diagnosis of Dementia in Men With Prostate Cancer.
Ravishankar Jayadevappa,Ravishankar Jayadevappa,Sumedha Chhatre,S. Bruce Malkowicz,Ravi B. Parikh,Thomas J. Guzzo,Alan J. Wein +6 more
TL;DR: Clinicians must carefully weigh the long-term risks and benefits of exposure to androgen deprivation therapy in patients with a prolonged life expectancy and stratify patients by dementia risk prior to androgens deprivation therapy initiation.
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A Phase 2 Randomized Controlled Trial of Personalized Peptide Vaccine Immunotherapy with Low-dose Dexamethasone Versus Dexamethasone Alone in Chemotherapy-naive Castration-resistant Prostate Cancer
Kazuhiro Yoshimura,Takafumi Minami,Masahiro Nozawa,Takahiro Kimura,Shin Egawa,Hiroyuki Fujimoto,Akira Yamada,Kyogo Itoh,Hirotsugu Uemura +8 more
TL;DR: PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC, and promising evidence of clinical benefit for peptide vaccines is provided.
Journal ArticleDOI
Sipuleucel-T in the treatment of prostate cancer: an evidence-based review of its place in therapy
Julie N. Graff,Erin Chamberlain +1 more
TL;DR: The process of creating the sipuleucel-T product from the manufacturing and patient aspects is described and the three RCTs in metastatic castration-resistant prostate cancer showed improved overall survival without meaningful decreases in symptoms, tumor volumes, or prostate-specific antigen levels are discussed.
Journal ArticleDOI
Phase Ib dose-finding study of abiraterone acetate plus buparlisib (BKM120) or dactolisib (BEZ235) in patients with castration-resistant prostate cancer.
Christophe Massard,Kim N. Chi,Daniel Castellano,Johann S. de Bono,Gwenaelle Gravis,Luc Dirix,Jean-Pascal Machiels,Alain C. Mita,Begoña Mellado,Sabine Turri,Joan Maier,Denes Csonka,Arunava Chakravartty,Karim Fizazi +13 more
TL;DR: No further study is planned for either buparlisib or dactolisib in combination with AA in CRPC, based on the assessment of available pharmacokinetics, safety, and efficacy data.
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