Concurrent use of corticosteroids was associated with worse outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) who were treated with enzalutamide, according to an analysis published in Clinical Cancer Research.1

Researchers conducted a post hoc analysis of data from the phase 3 AFFIRM trial (ClinicalTrials.gov Identifier: NCT00974311), which was designed to compare enzalutamide with placebo in mCRPC patients who had previously received docetaxel.

Prior results from the trial showed that enzalutamide significantly improved overall survival (OS), radiographic progression-free survival (rPFS), and time to prostate-specific antigen progression (TTPP).2


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In the posthoc analysis, researchers evaluated the impact of corticosteroid use on OS, rPFS, and TTPP. The analysis included 1199 patients who were randomly assigned 2:1 to receive enzalutamide (160 mg/day) or placebo.

In both arms, 30% of patients were already taking corticosteroids at baseline. While on study, 45% of patients in the placebo arm and 48% in the enzalutamide arm were prescribed corticosteroids. The most frequently used corticosteroids were prednisone/prednisolone and dexamethasone.

When compared with patients who did not receive corticosteroids, those who were taking corticosteroids at baseline had inferior OS, rPFS, and TTPP, regardless of treatment arm.

The median OS was 10.8 months for corticosteroid users and was not reached for nonusers (hazard ratio [HR], 2.13; 95% CI, 1.79-2.54; P <.0001). The median rPFS was 5.2 months and 8.0 months, respectively (HR, 1.49; 95% CI, 1.29-1.72; P <.0001). The median TTPP was 4.6 months and 5.7 months, respectively (HR, 1.50; 95% CI, 1.25-1.81; P <.0001).

In a multivariate analysis, baseline corticosteroid use was independently associated with decreased OS (HR, 1.71; 95% CI, 1.43-2.04; P <.0001) and rPFS (HR, 1.28; 95% CI, 1.11-1.48; P =.0007).

The researchers noted that patients derived benefit from enzalutamide treatment independently of corticosteroid use, but corticosteroid use was associated with worse baseline prognostic factors and outcomes.

Based on these findings, the researchers wrote that “physicians should consider carefully whether the potential benefit of corticosteroid use outweighs the potential risk of treatment-associated adverse events and the possibility of an inferior clinical outcome.”

Disclosures: This research was partly supported by Pfizer Inc. and Astellas Pharma, Inc., the codevelopers of enzalutamide. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

  1. Zhao JL, Fizazi K, Saad F, et al. The effect of corticosteroids on prostate cancer outcome following treatment with enzalutamide: A multivariate analysis of the phase III AFFIRM trial. Clin Cancer Res. Published online December 29, 2021. doi:10.1158/1078-432.CCR-21-1090
  2. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187-97. doi:10.1056/NEJMoa1207506