(Prostate Cancer) Treatment Sequence of Xtandi and Zytiga?
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This article is a summary of international medical information and is not medical advice; it cannot replace the diagnosis or treatment plan of your attending physician. The medical technologies, drug information and clinical data presented here are compiled from public literature and official statements of major Japanese medical institutions; the applicability and outcome of any therapy vary with each patient and must be assessed individually by a qualified physician.
On November 11, 2019, Daniel J. Khalaf published in the medical journal The Lancet the efficacy and safety results of sequentially using androgen receptor inhibitors Xtandi (enzalutamide) and Zytiga (abiraterone acetate) in patients with metastatic castration-resistant prostate cancer in a Phase II crossover clinical trial.
This Phase II crossover trial randomized patients with metastatic castration-resistant prostate cancer (N=202) into two groups based on treatment order. The primary endpoints were PSA progression-free interval and PSA response rate during second-line treatment.
Group A (Zytiga 1000 mg once daily + Prednisone 5 mg twice daily until PSA progression, then Xtandi 160 mg once daily; N=101)
Group B (Xtandi 160 mg once daily until PSA progression, then Zytiga 1000 mg once daily + Prednisone 5 mg twice daily; N=101)
The trial was initiated because both Xtandi and Zytiga are standard treatments for metastatic castration-resistant prostate cancer, but there has been no clear guidance on which drug to use first. Against this background, a trial was conducted to evaluate the optimal sequencing of androgen receptor inhibitor therapy.
Results: The primary endpoint — median PSA progression-free interval during second-line treatment — was: Group A 19.3 months vs. Group B 15.2 months. Group A showed a 34% reduction in PSA progression risk, with a hazard ratio of 0.66. Second-line PSA response rates were: Group A 36% (N=26) vs. Group B 4%.
Regarding safety, the incidence of Grade 3/4 adverse events observed in the majority of patients was: hypertension (Group A 27% / Group B 18%), fatigue (Group A 10% / Group B 4%). Serious adverse event rates were: Group A 15% / Group B 20%. No patients died from adverse events.
Based on the Phase II trial results, Daniel J. Khalaf concluded: For patients with metastatic castration-resistant prostate cancer, in terms of clinical benefit from sequencing androgen receptor inhibitors, starting with Zytiga before Xtandi may be preferable.
Source: Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial (Lancet Oncol. 2019 Nov 11. pii: S1470-2045(19)30688-6.)
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