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Enzalutamide exhibited high PSA response rate, similar efficacy to castration
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CHICAGO — Enzalutamide monotherapy for the treatment of hormone-naive prostate cancer produced a high PSA response rate and a marked PSA decline, according to results of a phase 2 trial presented at the ASCO Annual Meeting.
Tumor response levels — assessed by PSA levels and objective response rate — were consistent with castration.
Matthew R. Smith
Matthew R. Smith, MD, PhD, of Massachusetts General Hospital Cancer Center, and colleagues enrolled 67 patients with hormone-naive prostate cancer in the open-label, single-arm trial to evaluate the effectiveness of enzalutamide (Xtandi, Astellas Pharma), an oral androgen receptor inhibitor.
All patients were eligible for treatment with androgen deprivation therapy. They all had a noncastrate testosterone level of at least 230 ng/dL, a PSA of at least 2 ng/mL, an ECOG performance status of 0 and a life expectancy of more than 1 year at screening.
Patients received 160 mg enzalutamide daily for 24 weeks. The efficacy analysis was performed after 25 weeks; patients who exhibited clinical benefit at 25 weeks were permitted to continue treatment until disease progression or toxicity.
The primary endpoint of the study was a PSA response demonstrated by at least 80% decline at week 25. Secondary endpoints included endocrine levels, pharmacokinetics, safety and metabolic changes, such as bone composition, bone biomarkers, lipids and glycemic profiles.
At 25 weeks, the PSA response rate was 92.5% (95% CI, 86.2-98.8), and the median PSA decrease was –99.6% (95% CI, –100 to –86.5).
The primary endpoint was achieved in 62 of 67 patients, with a fairly constant PSA decline observed between patients with and those without metastases. Researchers reported a PSA decline of at least 80% in 93% of patients who exhibited metastasis at screening and in 92% of those who exhibited no metastasis.
“Enzalutamide monotherapy achieved a high PSA response rate and marked PSA decline. The measurable disease response rate was 50%,” Smith said. “These results compare favorably with that expected with androgen deprivation therapy. In contrast to castration, enzalutamide monotherapy was associated with stable bone mineral density and only modest changes in serum cholesterol and triglycerides.”
The most common adverse events were grade 1. They included gynecomastia (36%), fatigue (34%), nipple pain (19%) and hot flushes (18%). Five patients exhibited serious adverse events, but none were drug related.
“The observed endocrine changes and adverse effects are consistent with potent androgen receptor inhibition,” Smith said. “The results of this phase 2 study support the further evaluation of enzalutamide as monotherapy in prostate cancer.”
For more information:
Smith MR. #5001. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.
Disclosure: Smith reports consulting fees/honorarium from Aragon Pharmaceuticals, Astellas Pharma, Janssen Pharmaceuticals, Medivation and Millennium Pharmaceuticals.