enzalutamide

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NICE Guidance: Enzalutamide for treating metastatic hormone-relapsed prostate cancer before chemotherapy is indicated

August 22, 2017/by admin Z.9

Overview

Evidence-based recommendations on enzalutamide (Xtandi) for treating metastatic, hormone-relapsed prostate cancer for people in whom chemotherapy is not yet clinically indicated.

Summary of Appraisal Committee’s Key Conclusions

TA377	Appraisal title: Enzalutamide for treating metastatic hormone-relapsed prostate cancer before chemotherapy is clinically indicated	Section
Key conclusion
Enzalutamide is recommended, within its marketing authorisation, as an option for treating metastatic hormone-relapsed prostate cancer: in people who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated and only when the company provides it with the discount agreed in the patient access scheme. The Committee concluded that, with its preferred assumptions, the resulting incremental cost-effectiveness ratio (ICER) for enzalutamide compared with best supportive care was likely to be between £31,600 and £34,800 per quality-adjusted life year (QALY) gained. This range was dependent on the method used to adjust survival estimates for active treatments not used in the NHS. Furthermore, it was likely to be nearer to the lower end of this range. The Committee concluded that enzalutamide is innovative, and that taking into account factors, which had not been fully accounted for in the modelling, agreed that the ICER for enzalutamide compared with best supportive care was below £30,000 per QALY gained, and enzalutamide could be considered a cost-effective use of NHS resources.		1.1, 4.15, 4.18, 4.19
Current practice
Clinical need of patients, including the availability of alternative treatments	Enzalutamide is a well-tolerated treatment, and people welcome having more treatment options to delay cytotoxic chemotherapy. Enzalutamide and abiraterone (taken before chemotherapy is clinically indicated) are currently available through the Cancer Drugs Fund. Although abiraterone before docetaxel is available to some people, it is not embedded within current NHS funding arrangements because its future is not guaranteed. It was therefore not considered as a comparator. There are some people who can have enzalutamide but not abiraterone in clinical practice (people who can’t take corticosteroids, people with visceral disease and people with severe liver disease).	4.4, 4.1, 4.2, 4.18
The technology
Proposed benefits of the technology How innovative is the technology in its potential to make a significant and substantial impact on health-related benefits?	Enzalutamide is the preferred treatment option for people with visceral disease and liver dysfunction, in whom abiraterone is contraindicated at this position in the treatment pathway, or for people who can’t take corticosteroids. Although enzalutamide is not a new treatment, it is the only treatment that can give these benefits at this position in the treatment pathway and so is innovative.	4.18
What is the position of the treatment in the pathway of care for the condition?	Enzalutamide is indicated for people with metastatic hormone-relapsed prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy, before chemotherapy is indicated.	4.1
Adverse reactions	Enzalutamide is a well-tolerated treatment.	4.4
Evidence for clinical effectiveness
Availability, nature and quality of evidence	The efficacy estimates for enzalutamide came from PREVAIL. Enzalutamide increased overall survival (OS) compared with placebo. The Committee considered that adjusting the OS estimated from the trial for subsequent life-extending treatments taken by people in the trial, but which are not available in the UK, was appropriate.	4.6
Relevance to general clinical practice in the NHS	The Committee was aware that in PREVAIL, once the disease progressed, people on enzalutamide could move on to subsequent treatments. It was also aware that the company considered that some of these treatments (such as abiraterone, enzalutamide, cabazitaxel, sipuleucel-T, cytotoxic chemotherapy other than docetaxel and investigational treatments) would not be used in England at this position in the treatment pathway. The Committee agreed that it was appropriate to adjust the survival estimates for people having these treatments.	4.6
Uncertainties generated by the evidence	The extent of adjustment needed to the OS estimates (to account for subsequent treatments that people had in PREVAIL that are not available in clinical practice in England) was uncertain. It was unclear which of the methods the company had used for adjustment (the Inverse Probability of Censoring Weights or the two-stage method) was better, however IPCW was associated with fewer assumptions.	4.7
Are there any clinically relevant subgroups for which there is evidence of differential effectiveness?	None identified.	–
Estimate of the size of the clinical effectiveness including strength of supporting evidence	Enzalutamide increased OS compared with placebo, but the extent of the difference was uncertain because some people went on to have further active treatments in both study arms. The company tried to adjust for this but there was uncertainty about which method of adjustment was appropriate.	4.6, 4.7
Evidence for cost effectiveness
Availability and nature of evidence	The company developed a new model and needed to extrapolate OS and time to treatment discontinuation from the trial data in its model.	4.9. 4.11, 4.12
Uncertainties around and plausibility of assumptions and inputs in the economic model	The model structure was appropriate in terms of the sequence of treatments people would have in clinical practice in England, but there was uncertainty about whether time spent on treatments after enzalutamide reflected clinical practice. The Committee was concerned that that the company had not further checked the validity of the extrapolated data. This was particularly important because of the immaturity of the trial data and because of the small population at risk at the end of the trial follow-up (those who had not died or had been otherwise censored). This meant that a large proportion of the estimated survival benefit was based on the extrapolated period rather than the trial data.	4.9, 4.11
Incorporation of health-related quality-of-life benefits and utility values Have any potential significant and substantial health-related benefits been identified that were not included in the economic model, and how have they been considered?	The Committee considered whether the model captured the benefits of delaying chemotherapy, which is important to patients. The Committee agreed that the model predicted that people having enzalutamide had more time with better utility than people on best supportive care, but it was unclear whether the benefit of delaying chemotherapy had been fully captured by the utility values included in the modelling. The Committee concluded that enzalutamide is innovative.	4.18, 4.19
Are there specific groups of people for whom the technology is particularly cost effective?	None.	–
What are the key drivers of cost effectiveness?	The data cut-offs from PREVAIL that are used in the modelling and the utility value estimates.	4.11, 4.12, 4.13
Most likely cost-effectiveness estimate (given as an ICER)	The most plausible ICER for enzalutamide compared with best supportive care was nearer to £31,600 than to £34,800 per QALY gained. The Committee also concluded that enzalutamide is innovative and taking into account factors, which had not been fully accounted for in the modelling, agreed that the ICER for enzalutamide compared with best supportive care was below £30,000 per QALY gained.	4.15, 4.18, 4.19
Additional factors taken into account
Patient access schemes (PPRS)	The company has agreed a patient access scheme with the Department of Health. The level of the discount is commercial in confidence. The Department of Health considered that this patient access scheme would not constitute an excessive administrative burden on the NHS. The company revised its patient access scheme over the course of this appraisal to increase the discount to the cost of enzalutamide for the NHS.	2.3, 4.14
End-of-life considerations	The company did not make a case for enzalutamide meeting end-of-life criteria. The Committee considered that the first criterion for end of life (the treatment is indicated for patients with a short life expectancy, normally <24 months) had not been met. Therefore, the Committee did not consider the other criteria and concluded that enzalutamide did not meet end-of-life criteria for treating metastatic hormone-relapsed prostate cancer in people for whom chemotherapy is not yet indicated.	4.17
Equalities considerations and social value judgements	No equality issues were raised.	–

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Article of the Month: Is there an anti-androgen withdrawal syndrome with enzalutamide?

March 4, 2015/by admin Z.9

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Is there an anti-androgen withdrawal syndrome with enzalutamide?

Alejo Rodriguez-Vida¹, Diletta Bianchini², Mieke Van Hemelrijck³, Simon Hughes¹, Zafar Malik⁴, Thomas Powles⁵, Amit Bahl⁶, Sarah Rudman¹, Heather Payne⁷, Johann de Bono² and Simon Chowdhury^1,*

1 Guy’s and St Thomas’ NHS Foundation Trust, Great Maze Pond, London, UK, 2 Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK, 3 King’s College London, Division of Cancer Studies, Cancer Epidemiology Group, London, UK, 4 Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, UK, 5 St. Bartholomew’s Hospital NHS Foundation Trust, London, UK, 6 University Hospitals Bristol NHS Foundation Trust, Bristol, UK, 7 University College Hospital, London, UK

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OBJECTIVE

To examine prostate-specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.

METHODS

We retrospectively identified 30 consecutive patients with metastatic prostate cancer who were treated with enzalutamide after docetaxel. Post-discontinuation PSA results were available for all patients and were determined at 2-weekly intervals until starting further anticancer systemic therapy. PSA withdrawal response was defined as a PSA decline by ≥50% from the last on-treatment PSA, with a confirmed decrease ≥3 weeks later. Patient characteristics were evaluated in relation to the AAWS using univariate logistic regression analysis.

RESULTS

The median (range) patient age was 70.5 (56–86) years and the median (range) follow-up was 9.0 (0.5–16) months. The most common metastatic sites were the bone (86.7%) and lymph nodes (66.7%). Most patients (70%) had previously received abiraterone and 12 patients (40%) had also received cabazitaxel. The median (range) treatment duration with enzalutamide was 3.68 (1.12–21.39) months. PSA levels after enzalutamide withdrawal were monitored for a median (range) time of 35 (10–120) days. Only one patient (3.3%) had a confirmed PSA response ≥50% after enzalutamide discontinuation. One patient (3.3%) had a confirmed PSA response of between 30 and 50% and another patient (3.3%) had an unconfirmed PSA response of between 30 and 50%. The median overall survival was 15.5 months (95% CI 8.1–24.7). None of the factors analysed in the univariate analysis were significant predictors of PSA decline after enzalutamide discontinuation.

CONCLUSIONS

This retrospective study provides the first evidence that enzalutamide may have an AAWS in a minority of patients with metastatic castration-resistant prostate cancer. Further studies are needed to confirm the existence of an enzalutamide AAWS and to assess its relevance in prostate cancer management.

Editorial: Enzalutamide withdrawal syndrome: is there a rationale?

March 4, 2015/by Alessandra Mosca

Enzalutamide is a second generation non-steroidal antiandrogen (AA), which significantly improved overall survival (OS) and progression-free survival (PFS) after docetaxel (AFFIRM study), and OS and radiographic PFS before chemotherapy (PREVAIL study) in patients with metastatic castration-resistant prostate cancer (mCRPC) [1].

Being a potent androgen receptor (AR) antagonist, an enzalutamide withdrawal syndrome (EWS) appeared unlikely [2,3]. In contrast with this position, and considering the well-known AR structural alterations in CRPC, very recent preclinical and clinical data support the possibility of the existence of an EWS after the discontinuation of this drug, in a castration-resistant setting.

In patients with mCRPC progressing on androgen-deprivation therapy (ADT), the AAWS, due to the interruption of first generation AAs (flutamide, bicalutamide, nilutamide, cyproterone acetate and megestrol acetate), often pursues as a further hormonal manipulation, although no level one studies supported its efficacy. AAWS leads to a PSA reduction in 15–30% of patients, with concomitant symptomatic relief and radiographic responses in some cases, without impacting on survival [1]. The molecular mechanisms of the AAWS are still unclear. One of the possible mechanisms responsible for the AAWS is the mutation of the AR. In vitro models showed that bicalutamide may switch from antagonist to agonist in LNCaP-cxD cell lines, due to an additional AR mutation in codon 741 during bicalutamide treatment [4]. Similarly, preclinical in vitro and in vivo studies demonstrated that initially enzalutamide exerts its AR antagonist activity, but during the treatment enzalutamide potently induces an AR mutation, leading to the mutant ARF876L, which confers agonism to enzalutamide, and resistance to enzalutamide therapy [1]. In the clinical setting, the first evidence of possible EWS has begun to appear. Phillips [5] observed EWS in one patient, 40 days after enzalutamide discontinuation. Rodriguez-Vida et al. [1] showed EWS in three of 30 (10%) patients with mCRPC after the drug cessation, although none of the 17 factors examined were statistically significant predictors of PSA decline after enzalutamide interruption. Considering the clinical characteristics of the three patients showing EWS, interestingly all of them were aged <70 years, had Gleason score ≥7, had bone and/or lymph node metastases without visceral sites of disease, and had had previous treatments with bicalutamide and docetaxel. In all three patients, EWS seems to have no correlation with: prostate cancer staging at diagnosis (M0 vs M1), PSA value before enzalutamide, PSA decline on enzalutamide treatment, LHRH analogues and enzalutamide therapy duration. Similarly to bicalutamide WS, in all three patients no symptomatic improvement was recorded during EWS.
Focusing on patient 1, interestingly he displayed initially a PSA response during enzalutamide and later a further PSA decline plus radiological response after enzalutamide interruption (i.e. EWS), showing a sensitivity either to initial enzalutamide antagonism and to subsequent agonism, and exhibiting an EWS not preceded by a bicalutamide WS. This supports previous data concerning different AR mutations for the two different AAs, without subsequent clinical correlations between the two different AAWSs. A LHRH analogue duration treatment (5 months) shorter than a subsequent enzalutamide duration therapy (21.4 months) suggests different tumoral cells sensitivity to different ADTs, in different stages (hormone naïve and castration-resistant prostate cancer), likely related to several AR structural alterations collected along the disease. Intriguingly, patient 3 discontinued enzalutamide after only 1.2 months, maybe due to primary resistance [6]; nevertheless, he showed a PSA
response after enzalutamide interruption, suggesting that EWS, characterised by the switch from enzalutamide antagonism to agonism, could occur even in prostate cancer patients primary resistant to this drug. Limitations of the two first clinical reports related to EWS include a restricted sample size, a reduced number of EWS events and a short duration of follow-up after enzalutamide discontinuation. Furthermore, preclinical studies on EWS and published data concerning AAWS described more frequently early stage mCRPC, while the two papers considered heavily pretreated patients with mCRPC, in whom EWS incidence could be reduced due to several previous treatments, which probably produced various AR alterations.

In conclusion, the preclinical models have demonstrated one possible plausible mechanism responsible for EWS and enzalutamide resistance. First clinical reports suggest the possibility of EWS in a minority of patients after enzalutamide discontinuation in mCRPC. Further studies are needed to confirm and detail the EWS, before translating these data into clinical practice.

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Alessandra Mosca
Medical Oncology, ‘Maggiore della Carità’ University Hospital, Novara, Italy

References

1 Rodriguez-Vida A, Bianchini D, Van Hemelrijck M et al. Is there an antiandrogen withdrawal syndrome with enzalutamide? BJU Int 2015; 115: 373–80

2 von Klot CA, Kramer MW, Böker A et al. Is there an anti-androgen withdrawal syndrome for Enzalutamide? World J Urol 2014; 32: 1171–6

3 von Klot CA, Kuczyk MA, Merseburger AS. No androgen withdrawal syndrome for enzalutamide: a report of disease dynamics in the postchemotherapy setting. Eur Urol 2014; 65: 258–9

4 Hara T, Miyazaki J, Araki H, Yamaoka M, Kanzaki N, Kusaka M. Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndrome. Cancer Res 2003; 63: 149–53

5 Phillips R. An enzalutamide antiandrogen withdrawal syndrome. Nat Rev Urol 2014; 11: 366

6 Efstathiou E, Titus M, Wen S et al. Molecular characterization of Enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol 2015; 67: 53–60

Article of the Week: Enzalutamide in European and North American men participating in the AFFIRM trial

January 28, 2015/by admin Z.9

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Axel Merseburger discussing his paper.

If you only have time to read one article this week, it should be this one.

Enzalutamide in European and North American men participating in the AFFIRM trial

Axel S. Merseburger, Howard I. Scher†, Joaquim Bellmunt‡, Kurt Miller§, Peter F.A. Mulders¶, Arnulf Stenzl**, Cora N. Sternberg††, Karim Fizazi‡‡, Mohammad Hirmand§§, Billy Franks¶¶, Gabriel P. Haas¶¶, Johann de Bono*** and Ronald de Wit†††

Medizinische Hochschule Hannover, Hannover, §Charité – Universitätsmedizin Berlin, Berlin, **Universitätsklinikum Tübingen, Tübingen, Germany; †Memorial Sloan-Kettering Cancer Center, New York, NY, ‡Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, §§Medivation, Inc., San Francisco, CA, ¶¶Astellas Scientific and Medical Affairs, Inc., Northbrook, IL, USA; ¶Radboud University Nijmegen Medical Centre, Nijmegen, †††Erasmus University Medical Center, Rotterdam, The Netherlands; ††San Camillo – Forlanini Hospitals, Rome, Italy; ‡‡Institut Gustave Roussy, University of Paris Sud, Villejuif, France; ***Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK

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OBJECTIVE

To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311).

PATIENTS AND METHODS

Phase III, double-blind, placebo-controlled, multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis.

RESULTS

Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry.

CONCLUSION

This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions.

Editorial: Geography – an increasingly important variable in prostate cancer clinical trials

January 28, 2015/by Oliver Sartor

Enzalutamide is approved in the post-docetaxel phase for men with metastatic castrate-resistant prostate cancer (mCRPC) in North America (NA) and the European Union (EU). Merseburger et al. [1] now take a first look at comparing the efficacy and safety of enzalutamide in EU and NA patients treated in the AFFIRM trial. AFFIRM was a phase III double-blind, placebo-controlled multinational trial evaluating whether enzalutamide prolongs overall survival (OS) in men with mCRPC after docetaxel chemotherapy. This post hocexploratory analysis found a consistent OS benefit in both NA- and EU-treated patients. The safety profile was comparable in both regions.

Interestingly, the median OS appeared longer in the EU as compared with the NA cohort (‘not yet reached’ vs 17.4 months). With the placebo group in the EU the median survival was 16.2 vs 12.3 months in the NA cohort (3.9 months different). Direct statistical comparisons between regions were not performed but a median survival difference of 3.9 months is not inconsequential. Notably, drugs have been approved with lesser difference in OS.

The populations in AFFIRM have some baseline differences that may be of importance; the median time from diagnosis to randomisation was 68.9 months in the EU cohort vs 78.0 months in the NA cohort. Thus, it was possible that the NA cohort was ‘further along’ in the natural history of the disease despite apparently being well-balanced according to most baseline variables. The NA cohort was slightly more likely to have higher Gleason scores (50.6%) vs the EU cohort (44.0%), suggesting perhaps a slight difference in disease aggressiveness. It is also interesting that cardiac disease was present in 23.3% of the NA cohort vs only 7.2% of the EU cohort. Is it possible that cardiovascular diseases also contributed to a relative increase in mortality in the NA cohort? With regard to the post-protocol therapies, the use of abiraterone was more common in the EU cohort (30.5% of patients in the placebo group subsequently received abiraterone in the EU cohort vs 19.7% in the NA cohort). However, utilisation of cabazitaxel was more common in NA than in the EU (20.5% vs 9.9%). Some combination of pre-treatment and post-protocol variables in AFFIRM is probably the explanation for geographic variations in OS. Protocol treatments were well defined but these variables were not controlled.

These results in AFFIRM should also be considered in the context of geographic differences in medical care that may alter results and/or interpretation of phase III trials. Some of these differences have been previously documented in other phase III mCRPC trials. For instance, the recent phase III trials with orteronel reported no OS differences in the overall study [2]. However, in certain geographic regions (with less access to the newer life-prolonging drugs), the orteronel trials were clearly positive for the OS endpoint. In the TROPIC trial, cabazitaxel was associated with higher febrile neutropenia rates in some EU countries as compared with the USA. This was primarily due to geographic differences in prophylactic administration of granulocyte colony-stimulating factor (G-CSF) [3]. For the ALSYMPCA trial, striking geographic differences were noted in the timing (pre- or post-docetaxel) of radium-223 utilisation [4].

Understanding prognosis and treatment outcomes is increasingly critical in the design and interpretation of phase III clinical trials and particularly amongst trials that are designed to support regulatory approvals. Region or country where treatment takes place is an important variable to consider, especially if approved pre- and post-protocol treatments are not the same. This issue is even more important if the course of the disease is long (as in prostate cancer) and there are different treatments available from country to country.

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Oliver Sartor, Sumanta Kumar Pal*, Terhi Hermanson† and Charles L. Bennett‡,

Tulane Medical School, New Orleans, LA, *City of Hope Comprehensive Cancer Center, Duarte, CA, USA; † Helsinki University Central University, Helsinki, Finland; and ‡ College of Pharmacy, Medical University of South Carolina Cancer Center, Charleston, SC, USA

References

1 Merseburger AS, Scher HI, Bellmunt J et al. Enzalutamide in European and North American men participating in the AFFIRM trial. BJU Int 2015; 115: 41–9

2 Fizazi K, Jones R, Oudard S et al. Regional differences observed in the phase 3 trial (ELM-PC 5) with orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel. ASCO Meeting Abstracts. J Clin Oncol 2014; 32 (Suppl.): 5s (abstr 5042). Available at: https://meetinglibrary.asco.org/content/126314-144. Accessed November 2014

3 Ozguroglu M, Oudard S, Sartor AO et al. Effect of G-CSF prophylaxis on the occurrence of neutropenia in men receiving cabazitaxel plus prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in the TROPIC study. ASCO Meeting Abstracts. J Clin Oncol 2011; 29 (Suppl.): abstr 144. Available at: https://meetinglibrary .asco.org/content/72386-104. Accessed November 2014

4 Parker C, Nilsson S, Heinrich D et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013; 369: 213–23

Video: Enzalutamide in European and North American men participating in the AFFIRM trial

January 28, 2015/by admin Z.9

Enzalutamide in European and North American men participating in the AFFIRM trial

Read the full article

OBJECTIVE

To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311).

Tag Archive for: enzalutamide

Posts

Overview

Summary of Appraisal Committee’s Key Conclusions

Is there an anti-androgen withdrawal syndrome with enzalutamide?

OBJECTIVE

METHODS

RESULTS

CONCLUSIONS

Enzalutamide in European and North American men participating in the AFFIRM trial

OBJECTIVE

PATIENTS AND METHODS

RESULTS

CONCLUSION

Enzalutamide in European and North American men participating in the AFFIRM trial

OBJECTIVE

PATIENTS AND METHODS

RESULTS

CONCLUSION