Intermittent ADT: No significant advantage seen

St. Etienne, France-Intermittent androgen ablation proved feasible for patients with metastatic prostate cancer, but did not improve survival or quality of life compared with continuous hormonal therapy, investigators in a multicenter European study reported.

Median overall survival was about 4 years with maximum androgen suppression and about 3.5 years with intermittent therapy, a non-significant difference, said first author Nicolas A. Mottet, MD, a urologic oncologist at Clinique Mutualiste in St. Etienne, France. Progression-free survival showed a 6-month improvement with intermittent therapy, but the difference did not achieve statistical significance.

Scores on a standardized assessment of quality of life did not differ between treatment groups, either overall or in specific domains. The majority of patients treated with intermittent androgen ablation had testosterone recovery to normal levels during time off treatment, Dr. Mottet reported at the AUA annual meeting in Chicago.

The findings came from a 66-center study that Dr. Mottet characterized as the first randomized comparison of intermittent versus continuous maximum ablation in patients with metastatic prostate cancer. Inclusion criteria included a positive bone scan, Eastern Cooperative Oncology Group performance status <2, life expectancy >9 months, no prior treatment for metastatic prostate cancer, and PSA ≥20.0 ng/mL.

Eligible patients received 6 months of continuous androgen ablation consisting of flutamide (Eulexin), 750 mg/d, and leuprolide, 3.75 mg every 28 days. Patients who had no disease progression and PSA <4.0 ng/mL after 6 months were randomized to continuous or intermittent androgen ablation with the same regimen.

Patients assigned to intermittent therapy stopped treatment after the 6-month open-label phase of the study and remained off therapy until PSA increased to >10.0 ng/mL or clinical progression. At that point, maximum androgen ablation was resumed for 3 months or until PSA declined to <4.0 ng/mL. Patients then continued cycles on and off therapy.

All patients were followed at 3-month intervals until disease progression.

The randomized phase of the study included 169 patients. The primary endpoint was overall survival. Secondary outcomes included scores on the European Organization for Research and Treatment of Cancer Quality of Life (QLQ-C30) questionnaire, progression-free survival, and treatment tolerability.

Mean age was 69 years, mean testosterone level was about 4.0 ng/mL, and mean PSA was 633.0 ng/mL in patients randomized to continuous androgen ablation and 559.0 ng/mL in the intermittent therapy group (medians of 144.0 ng/mL and 181.0 ng/mL, respectively). Patients in the intermittent therapy group completed 15 cycles of therapy and were off treatment 49% of the time.

Median overall survival was 1,560 days with continuous therapy and 1,265 with intermittent therapy (p=.746). Median progression-free survival was 452 days with continuous treatment versus 620 with intermittent therapy (p=.736).

Scores on the QLQ-C30 did not differ significantly between groups. The frequency of side effects was 94% with continuous therapy and 84% with intermittent therapy. Hot flashes occurred in 64% and 60% of men, respectively, and bone pain was reported in 13% of both groups.

Dr. Mottet is a consultant/adviser for Takeda French Point.