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A randomized trial tested whether the addition of apalutamide, an androgen receptor blocker, to androgen-deprivation therapy might improve radiographic (including MRI-detected) progression–free survival and overall survival. Apalutamide was significantly more effective than placebo for both end points.

In this study, the androgen-receptor inhibitor enzalutamide improved progression-free and overall survival in men with castration-resistant metastatic prostate cancer who had not received chemotherapy. Prostate cancer is the most commonly diagnosed cancer and the sixth leading cause of cancer-related death among men worldwide. 1 Strategies to block androgen-receptor signaling have formed the backbone of prostate-cancer therapy since the first description of the hormonal dependence of this cancer in 1941. 2 Advances in endocrine therapies have improved survival in men with high-risk locoregional prostate cancer. 3 , 4 However, new hormonal agents have been shown to extend survival in men with metastatic castration-resistant disease. 5 – 9 In most patients who are treated for advanced recurrent prostate cancer with androgen-deprivation therapy (comprising a luteinizing hormone–releasing hormone [LHRH] analogue or orchiectomy with . . .

In this double-blind, placebo-controlled, 52-week trial among postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 μg of testosterone per day resulted in a significant although modest increase in the 4-week frequency of satisfying sexual episodes (1.4 more episodes per month), but the women were also subject to more adverse events, including androgenic side effects. In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 '1;g of testosterone per day resulted in a significant although modest increase in the 4-week frequency of satisfying sexual episodes. The literature suggests that the prevalence of sexual problems among women ranges from 9 to 43%. 1 – 4 Among these women, hypoactive sexual desire disorder is a commonly reported, symptom-driven condition characterized by a decrease or absence of interest in sexual activity, causing distress. 5 Decreased libido is common after natural menopause 6 , 7 and bilateral oophorectomy. 8 – 10 Several studies have shown the efficacy and short-term safety of a transdermal patch delivering 300 μg of testosterone per day for the treatment of hypoactive sexual desire disorder in women who have undergone either surgically induced or natural menopause and who use concomitant estrogen. 11 – . . .

The addition of abiraterone, a drug that blocks endogenous androgen synthesis, to standard androgen-deprivation therapy in patients with newly diagnosed, metastatic prostate cancer significantly increased overall survival, with a low rate of adverse effects.

A randomized trial involving patients with metastatic prostate cancer whose disease progressed after receipt of docetaxel and hormonal therapy showed that cabazitaxel was superior to an androgen-signaling–targeted agent in extending imaging-based progression-free survival, overall survival, and PSA response.

Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown. In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leuprolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety. A total of 1068 patients underwent randomization: 355 were assigned to the combination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metastasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metastasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzalutamide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P = 0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures. In patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with respect to metastasis-free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).

Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23–184). Median follow-up was 43 months (IQR 30–60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79–1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66–0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69–0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3–5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

The addition of abiraterone and prednisolone to standard androgen-deprivation therapy as the first treatment for patients with locally advanced or metastatic prostate cancer improved overall and failure-free survival, with a small increase in high-grade toxic effects.

Among men with nonmetastatic prostate cancer who had a rapid PSA doubling time and were receiving androgen-deprivation therapy, the median metastasis-free survival was 40.5 months with apalutamide versus 16.2 months with placebo. Rash occurred in 24% of men receiving apalutamide.

In this trial, the addition of six cycles of docetaxel to androgen-deprivation therapy resulted in longer median progression-free and overall survival than that with ADT alone in patients with metastatic prostate cancer. Regressions of metastatic prostate cancer were first documented in the 1940s and were achieved with surgical castration; subsequently, androgen-deprivation therapy (ADT) became the mainstay of therapy. 1 Attempts to improve the efficacy or decrease the treatment burden of ADT have included the use of antiandrogens alone, intermittent dosing of ADT, and the use of an antiandrogen combined with medical or surgical castration. 2 – 4 A meta-analysis revealed an increase in survival of 3 percentage points at 5 years with concurrent use of a nonsteroidal antiandrogen at the time of initiation of ADT. 2 However, resistance to ADT occurs in most patients, with the . . .