According to data to be presented at the upcoming meeting of the American Society of Clinical Oncology (ASCO), enzalutamide monotherapy substantially reduces PSA levels in androgen deprivation therapy (ADT)-naive patients with progressive or high-risk disease (including men with evident metastases).
The data to be presented by Smith et al. are from an open-label, Phase II, clinical trial of enzalutamide monotherapy at a dose of 160 mg/day for 25 weeks in men who had received no prior ADT of any type but who did require some form of androgen deprivation therapy. Eligible patients had to have a life expectancy of at least 1 year, a non-castrate serum testosterone level of ≥ 230 ng/dl, and an ECOG performance status of 0. The primary endpoint of the study was a reduction in the patients’ PSA levels of ≥ 80 percent compared to baseline at week 25 of therapy.
Here are the data provided in the study abstract (although additional data may actually be presented by Smith et al. at ASCO):
- 67 patients were enrolled in the trial.
- Average (median) patient age was 73 years.
- 26/67 patients (39 percent) had evident metastatic disease.
- 24/67 patients (36 percent had received earlier radical prostatectomies.
- 16/67 patients (24 percent) had received prior radiation therapy.
- Serum levels of enzalutamide reached a steady state after ~4 weeks.
- 62/67 patients (93 percent) met the prespecified 80 percent reduction in PSA levels at 25 weeks.
- The average (median) reduction in PSA level from baseline was actually –99.6 percent.
- Other average (mean) changes in metabolic outcomes at week 25 included:
- An increase in serum testosterone level of +114 percent
- An increase in serum estrogen level of +72 percent
- An increase in serum luteinizing hormone (LH) level of +185 percent
- A decrease in total body bone mineral density (BMD) of –0.24 percent
- A decrease in lean body mass of –4.15 percent
- An increase in fat body mass of +6.85 percent
- An increase in bone alkaline phoshoatase level of +14.75 percent
- An increase in total cholesterol level of +4.55 percent
- An increase in triglyceride level of +6.48 percent
- The most common treatment-emergent adverse events were all of Grade 1 and included:
- Gynecomastia in 24/67 patients (36 percent)
- Fatigue in 23/67 patients (34 percent)
- Nipple pain in 13/67 patients (19 percent)
- Hot flashes in 12/67 patients (18 percent).
- 5/67 patients (7 percent) had serious adverse events, but none of these show evidence of being drug related.
While this study clearly shows that enzalutamide monotherapy can induce a high rate of response in ADT-naive patients (as assessed by the decline in patients’ PSA levels over 25 weeks), and the level of adverse events observed appears to be relatively mild, we will need more information before clinicians can seriously consider enzalutamide therapy as a first-line option among high-risk, ADT-naive patients.
We will also need to know (a) the effects of other forms of therapy (e.g., LHRH agonists, antiandrogens, and drugs like abiraterone acetate) when used as second-line agents after first-line enzalutamide in patients like this and (b) whether the adverse events observed in response to enzalutamide in this brief (6-month) study are cumulative over a longer time-frame.