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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
Citations
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Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency.
Richard J. Auchus,Elizabeth O. Buschur,Alice Y. Chang,Gary D. Hammer,Carole A. Ramm,David Madrigal,George Wang,Martha Gonzalez,Xu Steven Xu,Johan W. Smit,James Jiao,Margaret K. Yu +11 more
TL;DR: AA 100-250 mg/d added to replacement hydrocortisone normalized several measures of androgen excess in women with classic 21OHD and elevated serum androstenedione.
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Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer.
Adam Sharp,Jon Welti,Maryou B K Lambros,David Dolling,Daniel Nava Rodrigues,Lorna Pope,Caterina Aversa,Ines Figueiredo,Jennifer Fraser,Zai Ahmad,Changxue Lu,Pasquale Rescigno,Pasquale Rescigno,Michael Kolinsky,Claudia Bertan,George Seed,Ruth Riisnaes,Susana Miranda,Mateus Crespo,Rita Pereira,Ana Ferreira,Gemma Fowler,Berni Ebbs,Penny Flohr,Antje Neeb,Diletta Bianchini,Antonella Petremolo,Semini Sumanasuriya,Alec Paschalis,Joaquin Mateo,Nina Tunariu,Wei Yuan,Suzanne Carreira,Stephen R. Plymate,Jun Luo,Johann S. de Bono +35 more
TL;DR: Liquid biopsies that determine circulating tumour cell androgen receptor splice variant-7 status have the potential to impact treatment decisions in metastatic castration-resistant prostate cancer patients and robust clinical qualification of these assays is required before their routine use.
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TL;DR: A spatial game (agent based continuous space) of mCRPC is developed that considers three distinct cancer cell types: those dependent on exogenous testosterone, those with increased CYP17A expression that produce testosterone and provide it to the environment as a public good (TP), and those independent of testosterone (T-).
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Abiraterone and Increased Survival in Metastatic Prostate Cancer
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