European Phase II Study Indicates Activity of Enzalutamide in Hormone-Naive Prostate Cancer


Key Points

  • Enzalutamide produced a PSA reduction ≥ 80% in 92.5% of patients.
  • Results were similar in patients with and without metastases.

As reported in The Lancet Oncology by Tombal et al, a single-arm phase II trial of the androgen receptor inhibitor enzalutamide (Xtandi) has shown that the agent is active in suppressing disease and well tolerated in men with hormone-naive prostate cancer.

In this ongoing trial, 67 men with hormone-naive prostate cancer for whom hormone therapy was indicated and who had noncastration levels of testosterone, prostate-specific antigen (PSA) levels ≥ 2 ng/mL, and Eastern Cooperative Oncology Group performance status of 0 received oral enzalutamide at 160 mg/d. The primary outcome measure was the proportion of patients with a decline of ≥ 80% in PSA at week 25.

PSA Responses

Overall, PSA decline ≥ 80% occurred in 62 patients (92.5%) at week 25, with responses being similar in those without metastases (n = 38, 93%) and with metastases (n = 26, 92%). For patients without and with metastases, PSA decline ≥ 90% occurred in 90% and 92%, 93% and 92% had PSA ≤ 4 ng/mL, and 49% and 39% had PSA ≤ 0.1 ng/mL. Of the 26 patients with metastases at baseline, 16 had measurable disease at baseline; of these, 3 (19%) had objective complete response, 5 (31%) had partial response, and 3 (19%) had stable disease.

Adverse Events

The most commonly reported adverse events of any grade were gynecomastia (36%), fatigue (35%), nipple pain (20%), and hot flush (18%). Grade 3 or higher adverse events occurred in 13% of patients, with those occurring in more than one patient consisting of hypertension (grade 3 in 4, 6%) and pneumonia (grade 3 in 2, 3%). Serious adverse events occurred in five patients (7%), with none considered related to treatment.

The investigators concluded, “Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer.”

Bertrand Tombal, MD, of Université Catholique de Louvain, Brussels, is the corresponding author for The Lancet Oncology article.

The study was funded by Astellas Pharma Inc and Medivation Inc. For full disclosures of the study authors, visit

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®.