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Xtandi Offers Small Benefits Over Zytiga in Advanced Prostate Cancer

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Researchers have compared Xtandi and Zytiga head-to-head in the treatment of metastatic castration-resistant prostate cancer.

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Xtandi Offers Small Benefits Over Zytiga in Advanced Prostate Cancer

Among patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with Xtandi (enzalutamide) was associated with improved survival outcomes that were described by researchers as “small but statistically significant” when compared to treatment with Zytiga (abiraterone acetate).

Researchers, publishing their findings in JAMA Network Open, noted Xtandi’s association with improvements to overall survival (OS; how long a patient lives, regardless of disease status), prostate cancer-specific survival (PCS; the percentage of patients who did not die of prostate cancer), time to treatment switching or death (TTS; time until a new prostate cancer treatment or death) and time to prostate-specific antigen (PSA; a protein associated with the presence of prostate cancer in the body) response (TTR; time until a PSA level decline of at least 50%).

Improvements, researchers wrote, were more prominent in the shorter-term outcomes such as TTS and TTR and among patients who had not received prior treatment with docetaxel chemotherapy or those who had a PSA doubling time of longer than three months.

The study included 5,779 patients with mCRPC who initiated treated in the United States Department of Veterans Affairs system between Jan. 1, 2014, and Oct. 30, 2022, with a median follow-up of between 38 and 60 months, according to the study.

“The findings of this large-scale observational study, with robust follow-up and rigorous methods, may provide guidance for making well-informed decisions about mCRPC treatment strategies,” researchers wrote in the study.

Learn More: Xtandi May Have Lower Infection Risk in Prostate Cancer Therapy

mCRPC is prostate cancer that has spread to other parts of the body and, according to the National Cancer Institute, keeps growing even when the testosterone levels in the patient’s body have been greatly reduced.

Xtandi, according to the National Cancer Institute, is intended to inhibit the activity of prostate cancer cell androgen receptors in order to reduce prostate cancer cell proliferation (when cells multiply quickly) and PSA levels. Zytiga, meanwhile, is designed to suppress testosterone production by the testes and adrenals to castrate-range levels, the National Cancer Institute explained.

“[Zytiga] and [Xtandi] are compounds that inhibit the androgen receptor signaling

pathway and are often used as first-line treatment for [mCRPC] instead of more toxic agents such as docetaxel,” researchers wrote. “While [Zytiga] and [Xtandi] are different in their mechanisms of action, toxicities and costs, both compounds are recommended for

mCRPC. Nevertheless, while both compounds are effective and widely used, their relative benefits and risks are still not fully understood. Each agent has been extensively studied in separate clinical trials including the pivotal trials leading to approval, but to our knowledge, they have not been [previously] compared in large-scale, head-to-head trials.”

Regarding OS, patients treated with Xtandi and Zytiga experienced restricted mean survival time (the mean survival time over a specific time period) of 24.29 months and 23.38 months, respectively, with a difference in restricted mean survival time of 0.9 months at four years. Restricted mean survival times at four years were 1.95 months for longer TTS and 3.57 months shorter for TTR. The restricted mean survival time at two years was 0.48 months longer for PCS.

More specifically, researchers found Xtandi to be associated with 1.14 months’ longer OS restricted mean survival time for patients who were not previously treated with docetaxel and 2.23 months’ longer for those who had a PSA doubling time of longer than three months.

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