Xtandi May Have Lower Infection Risk in Prostate Cancer Therapy

Patients with prostate cancer who were treated with Xtandi tended to have a lower rate of infection than those treated with Zytiga.

The utilization of Xtandi (enzalutamide), compared with Zytiga (abiraterone) — both in combination with androgen deprivation therapy — in the treatment of patients with prostate cancer may be associated with decreased incidence of sepsis, pneumonia and cellulitis or skin abscess, according to a retrospective study published in the journal Cancer.

“Within the armamentarium of metastatic (prostate cancer) management strategies, androgen receptor targeting agents, such as [Zytiga] and [Xtandi], have demonstrated overall survival benefits when added to androgen deprivation therapy,” the researchers wrote, adding that, despite evidence supporting efficacy and safety for both agents, high-quality evidence is limited to determine the optimal selection of the drugs.

“…Because of the lack of head‐to‐head comparison between these two drugs, it remains unknown as to whether the use of any of these drugs associates with more infections than the other.”

Therefore, in the retrospective study, the researchers aimed to determine if there was a difference in infection risk between Xtandi and Zytiga — in particular, the specific types of infection (sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections and tuberculosis), the time to the events and recurrent-event outcomes.

To do this, they identified patients with prostate cancer, aged 18 years or older, who underwent treatment with Xtandi or Zytiga, in combination with an androgen deprivation, in Hong Kong from December 1999 to March 2021. Patients were followed from the start of their treatment until September 2021, death or if they crossed over to another treatment.

In total, 1,582 patients were identified to follow for the study, including 923 patients who received Zytiga and 659 who were given Xtandi. Of note, 27.3% of the Zytiga arm and 16.7% of the Xtandi arm switched between the two treatments.

Patients who received Zytiga were on the drug for a median of 5.9 months, compared with 6.4 months in the Xtandi arm.

At baseline, patient characteristics didn’t vary much besides a higher prevalence of diabetes or antidiabetic use at baseline among those in the Xtandi group.

After a median follow-up of 10.6 months, the researchers discovered occurrences of sepsis (182 patients), pneumonia (229 patients), urinary tract infection (UTI; 174 patients), cellulitis or skin abscess (44 patients), central nervous system infection (three patients), and tuberculosis (two patients).

The incidence rates for infection to recur was highest in those who experienced sepsis, pneumonia and UTIs, followed by cellulitis or skin abscess and central nervous system infections.

When comparing between the 2 treatments, those who received Xtandi showed lower

cumulative incidences of sepsis, pneumonia and cellulitis or skin abscess, but not UTIs. These findings were similar when analyzing for recurrent infections to occur among both treatment arms.

“However, it should be noted that in patients with metastatic prostate cancer, the risk of UTI is typically multifactorial,” the researchers added.

The researchers acknowledged that the associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates.

Further, according to a subgroup analysis, treatment with Xtandi was associated with a lower risk for pneumonia and cellulitis or skin abscess among patients younger than 70 years. In addition, the agent was strongly associated with a lower risk for developing UTIs among those who reported with diabetes mellitus as baseline.

“This population‐based retrospective cohort study demonstrated that, despite higher diabetes prevalence, the [Xtandi] group had significant lower risks of sepsis, pneumonia and cellulitis or skin abscess, compared to [Zytiga] use among patients with (prostate cancer) receiving (androgen deprivation therapy,” the researchers concluded. “… further studies with detailed data on disease staging and hormone sensitivity

are warranted.”

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