Peter Iversen

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (141)455.88 Total impact

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    ABSTRACT: We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. ERG expression was assessed by immunohistochemistry (IHC) in 625 biopsy sets and 86 radical prostatectomy specimens from 265 patients with prostate cancer managed on active surveillance. For IHC, a rabbit monoclonal primary antibody was used (clone: EPR3864). TMPRSS2-ERG fluorescence in situ hybridisation (FISH) analyses were performed in 74 biopsies using the FISH ZytoLight TriCheck Probe (SPEC ERG/TMPRSS2). FISH results were correlated with IHC findings. The concordance between FISH and IHC was 97.3% and IHC demonstrated a sensitivity and specificity for ERG rearrangement of 100% and 95.5%, respectively. Applying IHC, 38.1% of patients were ERG-positive, 53.6% were ERG-negative and 8.3% showed both ERG-positive and negative tumour foci (ERG heterogeneous) at diagnosis. When ERG status was dichotomised (ERG-positive or heterogeneous vs ERG-negative), 95.6%-97.1% of patients did not experience ERG reclassification during the first two rounds of rebiopsies. The concordance in ERG status between biopsies and surgical specimen was 89.5%-94.2% depending on the number of rebiopsies included. Sampling bias was assumed to explain most (81.3%) of the mismatches in ERG status. Consistency in ERG status ranged from 90% to 95% for patients undergoing serial biopsies and radical prostatectomy. This indicates that biopsies can be used reliably to investigate ERG's prognostic and predictive value. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Clinical Pathology 06/2015; DOI:10.1136/jclinpath-2015-202894 · 2.55 Impact Factor
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    ABSTRACT: Castration-resistant prostate cancer (CRPC) is defined as tumour progression despite castrate levels of serum testosterone. During the past decade a number of new therapies, including chemotherapy and novel endocrine agents have been approved for CRPC treatment. The continued need for new effective drugs in CRPC has led to development of a novel therapeutic approach in CRPC treatment. Therapeutic vaccines activate the immune system to kill prostate cancer cells. This review describes recent pivotal phase 2 and 3 trials of CRPC vaccines and discusses the impact on future CRPC management.
    Ugeskrift for laeger 05/2015; 177(20).
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    ABSTRACT: Background Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC.Methods In total, 194 patients with advanced and/or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified on ERG-status. Risk reclassification and time-dependent area under the ROC curves were used to assess the discriminative ability of ERG-status. Time to PSA-nadir, proportion achieving PSA-nadir ≤0.2 ng/ml, and risk of PCa-specific death were secondary endpoints.ResultsMedian follow-up was 6.8 years (IQR: 4.9–7.3). In total, 105 patients (54.1%) were ERG-positive and 89 (45.9%) were ERG-negative. No difference in risk of CRPC was observed between ERG subgroups (P = 0.51). Median time to CRPC was 3.9 years (95%CI: 3.2–5.1) and 4.5 years (95%CI: 2.3-not reached) in the ERG-positive and ERG-negative group, respectively. Compared to a model omitting ERG-status, the ERG-stratified model showed comparable AUC values 1 year (77.6% vs. 78.0%, P = 0.82), 2 years (71.7% vs. 71.8%, P = 0.85), 5 years (68.5% vs. 69.9%, P = 0.32), and 8 years (67.9% vs. 71.4%, P = 0.21) from ADT initiation. No differences in secondary endpoints were observed.ConclusionsERG expression was not associated with risk of CRPC suggesting that ERG is not a candidate biomarker for predicting response to primary ADT in patients diagnosed with advanced and/or metastatic PCa. Prostate © 2015 Wiley Periodicals, Inc.
    The Prostate 05/2015; DOI:10.1002/pros.23026 · 3.57 Impact Factor
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    ABSTRACT: The objective of this study was to investigate the association between active surveillance (AS) progression criteria and histopathology features in subsequent radical prostatectomy (RP) specimens. Of 229 patients managed on AS, 80 patients underwent RP, of whom 68 met at least one of the following three progression criteria: progression on rebiopsy, short prostate-specific antigen (PSA) doubling time (PSAdt) and increase clinical tumour category (cT). Patients revealing histopathological features in the RP specimens involving GS ≥ 7 (3 + 4) were considered to have achieved a potential survival gain from the procedure (timely RP). The association between the progression criteria and timely RP was analysed using univariate logistic regression analyses. Of the 68 patients who met at least one of the progression criteria, 66% had timely RP features. Progression on rebiopsy was significantly associated with timely RP [odds ratio (OR) = 5.00, 95% confidence interval (CI) 1.51-16.51]. Although not statistically significant, progression defined by PSAdt was negatively associated with timely RP (OR = 0.36, 95% CI 0.13-1.00). Increase in cT showed no association with timely RP (OR = 1.17, 95% CI 0.35-3.87). A poor association was found between the progression criteria employed in the AS programme and histopathology features after subsequent RP. Only progression on rebiopsy was significantly associated with final histopathology.
    04/2015; DOI:10.3109/21681805.2015.1040448
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    ABSTRACT: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p=0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR=1.19 (95% CI: 1.00-1.43), p=0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care (n=991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment. Throughout the 14.6year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 04/2015; 51(10). DOI:10.1016/j.ejca.2015.03.021 · 4.82 Impact Factor
  • European Urology Supplements 04/2015; 14(2):e427. DOI:10.1016/S1569-9056(15)60420-1 · 3.37 Impact Factor
  • European Urology Supplements 04/2015; 14(2):e529. DOI:10.1016/S1569-9056(15)60522-X · 3.37 Impact Factor
  • European Urology Supplements 04/2015; 14(2):e323. DOI:10.1016/S1569-9056(15)60320-7 · 3.37 Impact Factor
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    ABSTRACT: Seminal plasma offer a more organ-specific matrix for markers in prostatic disease. We hypothesized that C-type natriuretic peptide (CNP) expression may constitute such a new target. Patients with benign prostatic hyperplasia, clinically localized and metastatic prostate cancer were examined for CNP and CNP precursor (proCNP) concentrations in blood and seminal plasma. Furthermore, CNP and the CNP receptor (NPR-B) mRNA contents in tissue from prostate and seminal vesicles were analyzed by qPCR. CNP and NPR-B concentrations decreased with increasing tumor burden (p = 0.0027 and p = 0.0096, respectively). In contrast, seminal plasma CNP and proCNP concentrations were markedly increased with increased tumor burden (p < 0.0001 and p < 0.0001, respectively). CNP/proCNP could be new markers in human prostate cancer.
    Biomarkers in Medicine 03/2015; 9(4):319-26. DOI:10.2217/bmm.14.74 · 2.86 Impact Factor
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    ABSTRACT: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. Open-label, single-arm study in patients with HNPC and noncastrate testosterone (≥230 ng/dl). Oral enzalutamide 160mg/d until disease progression or unacceptable toxicity. PSA response (≥80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk). The median (range) age was 73 (48-86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92-100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk. Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD. In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naïve prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. NCT01302041. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 02/2015; 65. DOI:10.1016/j.eururo.2015.01.027 · 12.48 Impact Factor
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    ABSTRACT: Abstract Objective. The aim of this study was to analyse relative survival, excess mortality and gain in life expectancy in men who underwent radical prostatectomy (RP) for localized prostate cancer (PCa) between 1995 and 2011 in Denmark. Material and methods. The study population comprised the complete cohort of 6489 men who underwent RP between 1995 and 2011. Risk of mortality was calculated using a competing risk model. Relative survival, excess mortality rate (EMR) and gain in life expectancy in men undergoing RP were calculated using a matched cohort Danish population based on date of birth and date of surgery. Results. During follow-up 328 patients died, 109 (33.2%) of PCa and 219 (66.8%) of other causes. The cumulative incidence of PCa mortality was 5.8% [95% confidence interval (CI) 4.4, 7.2] after 10 years. Relative survival was significantly above 1.0 for RP patients, except for high-risk patients. EMR was -9.34 (95% CI -10.56, -8.13) after 10 years, i.e. nine men would die in excess of the general population. Overall, the gain in life expectancy in men undergoing RP compared with the general population was 0.41 years. Conclusion. This population-based study demonstrated that the gain in life expectancy with RP compared with the general population in Denmark is minimal.
    12/2014; DOI:10.3109/21681805.2014.984324
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    ABSTRACT: Abstract Objective. Evidence supports active surveillance (AS) as a means to reduce overtreatment of low-risk prostate cancer (PCa). The consequences of close and long-standing follow-up with regard to outpatient visits, tests and repeated biopsies are widely unknown. This study investigated the trajectory and costs of AS in patients with localized PCa. Materials and methods. In total, 317 PCa patients were followed in a prospective, single-arm AS cohort. The primary outcomes were number of patient contacts, prostate-specific antigen (PSA) tests, biopsies, hospital admissions due to biopsy complications and patients eventually undergoing curative treatment. The secondary outcome was cost. Results. The 5 year cumulative incidence of discontinued AS in a competing-risk model was 40%. During the first 5 years of AS patients underwent a median of two biopsy sets, and patients were seen in an outpatient clinic including PSA testing three to four times annually. In total, 38 of the 406 biopsy sessions led to hospital admission and 87 of the 317 patients required treatment for bladder outlet obstruction (BOO). With a median of 3.7 years' follow-up, the total cost of AS was euro (€) 1,240,286. Assuming all patients had otherwise undergone primary radical prostatectomy, the cost difference favoured AS with a net benefit of €662,661 (35% reduction). Conclusions. AS entails a close clinical follow-up with a considerable risk of rebiopsy complication, treatment of BOO and subsequent delayed definitive therapy. This risk should be weighed against a potential economic benefit and reduction in the risk of overtreatment compared to immediate radical treatment.
    11/2014; DOI:10.3109/21681805.2014.970572
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    ABSTRACT: Background Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed. Objective To examine the association between ERG expression at diagnosis and the risk of progression during AS. Design, setting, and participants This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10–12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression. Outcome measurements and statistical analysis Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events. Results and limitations A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p < 0.0001) and of the subgroups PSA progression (p < 0.0001) and histopathologic progression (p < 0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3–29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7–68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62–3.72; p < 0.0001). The main limitation of this study is its observational nature. Conclusions In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes. Patient summary The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression.
    European Urology 11/2014; 66(5). DOI:10.1016/j.eururo.2014.02.058 · 12.48 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
    Nature Genetics 09/2014; 46(10). DOI:10.1038/ng.3094 · 29.65 Impact Factor
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    ABSTRACT: Objective To investigate the clinical implications of interobserver variation in the assessment of re-biopsies obtained during active surveillance (AS) of prostate cancer.Patients and Methods In all, 107 patients with low-risk prostate cancer with 93 diagnostic biopsy sets and 109 re-biopsy sets were included. The International Society of Urological Pathology 2005 Gleason scoring system was used for the histopathological assessment of all biopsies. Three different definitions of histopathological progression were applied. Unweighted and linear weighted Kappa (κ) statistics were used to compare the interobserver agreement.ResultsThe overall Gleason score agreement was 68.8% with a weighted κ of 0.670. The interobserver agreement was 79.6% for meeting the AS selection criteria. According to the three progression definitions applied, overall agreement was between 80.7% and 89.0% with weighted κ values of 0.746–0.791. Treatment recommendations would have changed in up to 10.1% (95% confidence interval 5.4–17.7%) of the 109 re-biopsy sets.Conclusion Kappa statistics showed strong agreement between the histological evaluations. However, up to 10% of patients on AS would receive a different treatment recommendation depending upon which histopathological evaluation of re-biopsies was used for treatment planning.
    BJU International 06/2014; 115(4). DOI:10.1111/bju.12820 · 3.13 Impact Factor
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    ABSTRACT: Background Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. Methods In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. Results The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment. Conclusions Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.)
    New England Journal of Medicine 06/2014; 371(5). DOI:10.1056/NEJMoa1405095 · 54.42 Impact Factor
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    ABSTRACT: To investigate how location of positive surgical margins (PSM) in pT2 tumors affect the risk of biochemical recurrence (BR). The study includes 1,133 consecutive patients from 1995 until end of 2011, who had organ-confined disease (pT2) following RP. The location of PSM was stratified into apical and non-apical. BR was defined as the first PSA ≥ 0.2 ng/ml after RP. Risk of BR was analyzed with Kaplan-Meier and Cox regression analysis. Median follow-up was 3.6 years (range: 0.5-15.5 years). The overall pT2 PSM rate was 26.3%. Overall, a pT2 with PSM had a 3.1-fold increased risk of BR compared to margin negative patients. Patients with pT2 apical and non-apical PSM had a 5-year biochemical recurrence-free survival of 84.9% (95% CI: 77.6-92.2%) and 78.6% (95% CI: 71.3-85.9%), respectively. In multivariate analysis, pT2 apical and non-apical PSM was individually associated with a 2.2- and 3.8-fold increased risk of BR compared to margin negative patients. In our cohort the location of pT2 PSM was associated with time to BR, that is, patients with non-apical pT2 PSM endured the highest risk of BR compared to apical PSM. This may indicate that not all patients with pT2 PSM should be offered adjuvant therapy. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 06/2014; 109(8). DOI:10.1002/jso.23573 · 2.84 Impact Factor
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    ABSTRACT: Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection for the AS strategy and how they should be managed within the program. However, uncertainties persists concerning optimal patient selection and reliable progression criteria, as well as the long-term safety of AS. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 06/2014; 109(8). DOI:10.1002/jso.23584 · 2.84 Impact Factor
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    ABSTRACT: INTRODUCTION AND OBJECTIVES: Enzalutamide (ENZA), an oral androgen receptor inhibitor, improved overall survival (OS) in mPC patients (pts) who had received prior docetaxel (Scher et al, NEJM 367:13, 2012). The PREVAIL study examined the impact of ENZA on OS and radiographic progression-free survival (rPFS) in asymptomatic or mildly symptomatic chemotherapy-naïve men with mPC that had progressed on androgen deprivation therapy (ADT). Based on statistically significant benefits for ENZA in OS and rPFS, the Data Monitoring Committee recommended stopping the study at the interim analysis. Here we report primary endpoint results and subgroup analyses of pts with and without visceral disease defined as liver and/or lung metastases. METHODS: In this double-blind, multinational study, pts were randomized 1:1 to ENZA 160 mg/day or placebo. OS and rPFS were coprimary endpoints. Planned sample size was 1680 with 765 deaths to achieve 80% power to detect a target OS hazard ratio (HR) of 0.815 with a 2-sided type I error rate of 0.049 and a single interim analysis at 516 (67%) deaths. Prespecified subgroup analyses evaluated OS and rPFS in pts with and without visceral disease and followed the same statistical methodologies as the protocol-specified analyses for all pts. Additional subgroup analysis of time to cytotoxic chemotherapy, a key secondary endpoint, was performed post hoc. RESULTS: A total of 1717 men were randomized (1715 treated), including 1513 pts (88.1%) without and 204 (11.9%) with visceral disease at screening (63.7% lung and 36.3% liver and/or lung). Pts without visceral disease had lower baseline median PSA than pts with visceral disease (46.8 and 72.5 ng/mL, respectively), better performance status (68.9% and 61.8% ECOG PS ¼ 0), less lymph node disease (49.8% and 57.8%), but similar rates of bone disease (83.7% and 80.4%). OS, rPFS, and time to chemotherapy results by subgroup are shown in the table. CONCLUSIONS: Treatment with enzalutamide significantly improved OS and rPFS in men with chemotherapy-naïve mPC. Though pts with visceral disease progressed more rapidly regardless of treatment allocation, the benefit of enzalutamide was consistent among pts with or without visceral disease.
    The Journal of urology 05/2014; 191(4S):e223. DOI:10.1016/j.juro.2014.02.2577 · 3.75 Impact Factor
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    ABSTRACT: The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. 67 men were enrolled into the study. 62 patients (92·5%, 95% CI 86·2-98·8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. 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. Astellas Pharma Inc, Medivation Inc.
    The Lancet Oncology 04/2014; 15(6). DOI:10.1016/S1470-2045(14)70129-9 · 24.73 Impact Factor

Publication Stats

2k Citations
455.88 Total Impact Points

Institutions

  • 1998–2015
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2013–2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 1998–2013
    • Rigshospitalet
      • Department of Urology
      København, Capital Region, Denmark
  • 2004
    • Technische Universität Dresden
      Dresden, Saxony, Germany
    • Medical College of Wisconsin
      • Department of Urology
      Milwaukee, Wisconsin, United States
    • Herlev Hospital
      Herlev, Capital Region, Denmark
  • 2002
    • Karolinska University Hospital
      • Department of Urology
      Tukholma, Stockholm, Sweden
  • 2000
    • Walter Reed National Military Medical Center
      Washington, Washington, D.C., United States
  • 1997
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark