Intermittent Androgen Monotherapy Is Noninferior to Maximal Androgen Blockade for Advanced PCa

FC Silva, FM Silva, F Gonçalves, A Santos, J Kliment, P Whelan, T Oliver, N Antoniou, S Pastidis, AM Queimadelos, C Robertson

Cancro prostataABSTRACT

BACKGROUND
Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa).

OBJECTIVE
To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB.

DESIGN, SETTING, AND PARTICIPANTS
This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa.

INTERVENTION
During induction, patients received CPA 200mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25mg) analogue plus CPA 200mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200mg/d plus monthly LHRH analogue).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded.

RESULTS AND LIMITATIONS
We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy.

CONCLUSIONS
Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

FC Silva, FM Silva, F Gonçalves, A Santos, J Kliment, P Whelan, T Oliver, N Antoniou, S Pastidis, AM Queimadelos, C Robertson

Locally Advanced and Metastatic Prostate Cancer Treated With Intermittent Androgen Monotherapy or Maximal Androgen Blockade: Results From a Randomised Phase 3 Study by the South European Uroncological Group

Eur Urol 2014 Aug 01;66(1)232-239,