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Second-Line Therapies May Benefit Patients With Castration-Resistant Prostate Cancer and Poor Performance Status

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Key Points

  • Patients with castration-resistant prostate cancer and a poor performance status who were previously treated with docetaxel may benefit from currently available second-line therapies.
  • Among these patients with a performance status ≥ 2, there was a significant reduction in the risk of death associated with currently available therapies for castration-resistant prostate cancer.
  • This reduction in the risk of death was confirmed for hormonal therapies in the second-line setting, but not for chemotherapy.

Patients with castration-resistant prostate cancer and a poor performance status who were previously treated with docetaxel may benefit from currently available second-line therapies, according to the findings of a meta-analysis by Iacovelli et al published in Prostate Cancer and Prostatic Diseases. Currently available therapies included abiraterone (Zytiga), cabazitaxel (Jevtana), and enzalutamide (Xtandi).

Study Methodology

Although the management of prostate cancer has been associated with improved outcomes with the widespread use of docetaxel therapy, some patients still progress to castration-resistant disease. It has been noted in the medical literature that approximately 20% of newly diagnosed patients have an Eastern Cooperative Oncology Group performance status ≥ 2. This percentage may be even higher in patents with castration-resistant disease. What impact this status may have on patient outcomes has not been widely studied.

The investigators evaluated the possible benefit of currently available treatments in patients with castration-resistant prostate cancer who previously received docetaxel-based therapy and had a performance status ≥ 2. They analyzed the medical records of 3,149 patients who had undergone participation in phase III clinical trials. Patients were divided into two groups based on performance status score: those with a score from 0 to 1 and those with a score of 2 or higher.

Patients participating in the clinical trials received abiraterone, cabazitaxel, enzalutamide, mitoxantrone, or placebo. Mitoxantrone represented the control treatment. Of the patients treated in the experimental arms, 19.5% received cabazitaxel, 39.8% received abiraterone, and 40.7% received enzalutamide. In the control arms, 67.7% of patients received placebo, and 32.3% received mitoxantrone.

Of the 185 patients in the experimental arms who had a performance status score ≥ 2, 17.8% were administered cabazitaxel, 44.3% were administered abiraterone, and 37.9% were administered enzalutamide. Of the 105 patients in the control arms who had a performance status score ≥ 2, 26.7% were given mitoxantrone, and 73.3% were given placebo.

Significant Findings

Taking into account the entire patient population and each of the experimental treatment modalities, there was a 26% to 37% decrease in the risk of death (hazard ratio [HR] = 0.69; 95% confidence interval [CI] = 0.63?0.76; P < .001). Among patients in the experimental arms with a performance status score ≥ 2, there was a 26% reduction in the risk of death compared with patients in the control arms (HR = 0.74; 95% CI = 0.56–0.98; P = .035).

In the subgroup analysis, which was based on the type of treatment the patients received, hormonal therapy was found to be more beneficial than chemotherapy. Among the hormonal therapies (abiraterone and enzalutamide), there was a reduction in the risk of death, which was not seen in patients receiving cabazitaxel. 

Clinical Implications

Currently, there are no established guidelines for continued treatment after the failure of docetaxel therapy in the minority of patients with poor performance status. The results from this study demonstrated the benefit in overall survival associated with currently available hormonal treatments such as abiraterone and enzalutamide in patients not eligible for second-line chemotherapy.

The investigators suggested that the available therapies for castration-resistant prostate cancer may be of benefit in patients regardless of their performance status. Still, the choice of which of these agents is the most effective choice of therapy remains dependent on patient characteristics, drug-toxicity profiles, and drug availability.

In closing, the investigators stated, “These results may improve clinical practice, encouraging the treatment of patients with [performance status 2] at the end of docetaxel therapy, even if the expected benefit from treatment needs to be balanced with possible adverse events due to therapy.”

Roberto Iacovelli, MD, of Sapienza University, Rome, is the corresponding author of the article in Prostate Cancer and Prostatic Diseases.

The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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