Prostate Cancer - Hormone-refractory patients still waiting for treatment breakthroughs
ABOUT DATAMONITOR HEALTHCARE
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About the Oncology pharmaceutical analysis team
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CHAPTER 1 EXECUTIVE SUMMARY
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Scope of the analysis
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Datamonitor insight into the prostate cancer market
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Contributing experts
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Related reports
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Upcoming reports
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CHAPTER 2 INTRODUCTION AND SCOPE
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Introduction
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Coverage of the Stakeholder Insight Survey
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Disease definition and epidemiology
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Patient segmentation
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Drug therapy for prostate cancer
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Recurrent prostate cancer
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Hormone-refractory prostate cancer
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Pipeline products for hormone-refractory prostate cancer
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CHAPTER 3 COUNTRY TREATMENT TREES
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Introduction
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Country treatment trees
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US
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Japan
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France
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Germany
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Italy
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Spain
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UK
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CHAPTER 4 DISEASE DEFINITION AND EPIDEMIOLOGY
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Definition of prostate cancer
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Prostate cancer
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The most common cancer type and second leading cause of cancer-related death in males
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Histology
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The majority of prostate tumors are adenocarcinomas
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Risk factors
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Older age
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Race
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Family history
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Hormones
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Dietary factors
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Symptoms
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Symptoms frequently occur only at an advanced stage of prostate cancer
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Screening and diagnosis
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Measurement of PSA has proved fairly useful in the detection of prostate cancer, however, several issues need to be resolved
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A widespread screening program exists in the US...
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...however, in Europe, results from the ERSPC trial are necessary before screening programs can be considered
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Though PSA screening has been shown useful in Japan, the practice is not widespread
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Staging
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Prostate cancer is staged using the TNM system and a histologically-based Gleason score
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Epidemiology of prostate cancer
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Incidence of prostate cancer
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Prostate cancer is a tumor associated with older men, therefore incidence is rising in line with the ageing population
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Mortality from prostate cancer
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Potentially asymptomatic disease and a high rate of fatality from co-morbidities mean mortality from prostate cancer is not especially high
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Prevalence of prostate cancer
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Prevalence is high given the tendency for early diagnosis and low mortality
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CHAPTER 5 PATIENT SEGMENTATION
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Introduction
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Staging of prostate cancer
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Staging at diagnosis
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Around half of all prostate cancer cases are diagnosed at a localized stage
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Staging at the time of survey
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A greater proportion have advanced-stage prostate cancer if patients at the time of survey are examined
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One-quarter of all prostate cancer patients have hormone-refractory disease
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Differences in staging
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Urologists encounter more early-stage patients, while medical oncologists typically treat advanced disease...
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...however, the difference is minimal in Japan due to its structure of medical practice
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CHAPTER 6 INITIAL DRUG THERAPY FOR PROSTATE CANCER
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Introduction
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Overview of initial therapy for prostate cancer
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Localized prostate cancer patients can undergo watchful waiting or radical prostatectomy
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Initial treatment of locally advanced and metastatic prostate cancer constitutes androgen deprivation therapy
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Initial treatment of prostate cancer
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Initial use of drug therapy
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As expected, use of initial drug therapy increases with an advancing stage of prostate cancer
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However, a higher than expected proportion of localized stage patients appear to receive drug therapy
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A lower proportion than average of locally advanced and metastatic prostate cancer patients receive initial drug therapy in the US
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Specific initial drug therapy of prostate cancer
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Across all stages of prostate cancer
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LHRH agonist monotherapy and total androgen blockade are the favored drug regimens used in the initial treatment of prostate cancer
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Localized prostate cancer
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LHRH agonist monotherapy is generally sufficient given that an aggressive approach is not needed while the tumor is localized...
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...however, in Spain and Japan, total androgen blockade is the favored initial treatment approach for localized prostate cancer
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Anti-androgen monotherapy is the third most frequently used drug regimen for localized tumors due to its lower efficacy than medical castration
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Use of cytotoxics with or without antihormonal therapy is very low in the initial treatment of localized prostate cancer
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Locally advanced prostate cancer
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On average, similar trends are seen in the initial treatment of locally advanced prostate cancer as for localized
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More locally advanced patients receive TAB than localized patients, at the expense of use of anti-androgen monotherapy
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Use of cytotoxics with or without antihormonal therapy is still low
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Advanced prostate cancer
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On average, the majority of advanced prostate cancer patients appear to receive the more aggressive total androgen blockade regimen as initial treatment, although this observation is deceptive
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More advanced disease which may require more aggressive treatment means the combination of cytotoxics and antihormonal therapy is the third preferred initial regimen
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Use of cytotoxics in the initial treatment of prostate cancer is relatively high across all stages in Germany
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LHRH agonist monotherapy
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Use of anti-androgens to counter testosterone flare
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Use of anti-androgens to prevent testosterone flare from LHRH agonists increases with a more advanced stage of prostate cancer
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Use of temporary anti-androgen therapy is, surprisingly, lowest in the US and Germany, and highest in the UK
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Use of specific LHRH agonists as monotherapy
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Leuprolide is the favored LHRH agonist for use as monotherapy across all stages of prostate cancer due to its availability in a variety of depot formulations
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Goserelin is the second preferred LHRH agonist monotherapy across all stages of prostate cancer
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Use of the various LHRH agonists varies greatly between countries, with use of leuprolide highest in the US and use of goserelin highest in the UK
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Anti-androgen monotherapy
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Use of specific anti-androgens as monotherapy
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Bicalutamide, in varying dosing formulations, is the leading anti-androgen for use as monotherapy across all stage of prostate cancer
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Despite being the only branded product in a heavily genericized market, Casodex (bicalutamide) remains the leader due to a number of advantages over its competition
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Casodex is by far the preferred anti-androgen for use as monotherapy in each of the seven major pharmaceutical markets
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Casodex 150mg has had a tumultuous regulatory pathway to date
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The EPC trial showed that 150mg Casodex daily is suitable for treatment of locally advanced prostate cancer, but not localized disease
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Casodex 150mg is still used in localized prostate cancer, according to surveyed physicians
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In Japan, only 80mg Casodex is available, while in the US, only 50mg Casodex is available
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In the EU, use of Casodex is more fragmented between the 50mg and 150mg formulations
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Use of flutamide is highest in the US
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Use of cyproterone and nilutamide are highest in the EU
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Total androgen blockade
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Use of specific total androgen blockade regimens
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A combination of leuprolide and bicalutamide is the top TAB regimen across all stages of prostate cancer
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No specific recommendations for TAB regimen are made, therefore the choice of agents is most likely due to physician preference or cost
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In the US and Japan, the top three TAB regimens do not vary by stage, with the leading combination constituting leuprolide and bicalutamide
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More variation is seen in the top three TAB regimens used in each of the five European countries, although leuprolide or goserelin with bicalutamide still emerge as the first or second preferred regimen in all markets
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Use of specific formulations of LHRH agonists
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Use of specific formulations as monotherapy or as part of combination regimens
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On average across the seven major markets, the three-month depot version of leuprolide is the leading formulation of LHRH agonist
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Three-month goserelin emerges as the second preferred formulation of LHRH agonist
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Three-month formulations of LHRH agonist are deemed to offer the most convenience and flexibility to patients
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In the US, use of alternative leuprolide formulations is favored
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Triptorelin and buserelin formulations appear in the top three preferred LHRH agonist formulations only in four of the EU countries
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CHAPTER 7 RECURRENT PROSTATE CANCER
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Introduction
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Overview of therapy for recurrent prostate cancer
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Treatment of recurrent prostate cancer typically involves further lines of antihormonal therapy
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Remission rates
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Remission rates by stage of disease
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Remission rates are surprisingly high in the more advanced stages of prostate cancer, indicating that systemic therapy may offer sufficient disease control
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High use of TAB to treat localized disease in Japan may result in a significantly higher remission rate in these patients
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Duration of remission
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Duration of remission is longest in localized prostate cancer patients and shortest in advanced patients
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A high proportion of localized patients are initially treated with drug therapy in Spain, thereby resulting in a higher duration of remission
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Relapse rates
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Patients who relapse following remission
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As expected, relapse rates are highest among advanced prostate cancer patients and lowest in localized disease
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Highest relapse rates in Spain, albeit for no apparent reason
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Stage of disease present at relapse
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Due to enhanced detection of rising PSA levels, relapsed disease can be identified while still at a localized stage
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Hormone-refractory disease at relapse
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Patients with more advanced disease may have more aggressive tumors, potentially placing them at a higher risk of developing hormone-refractory disease more quickly at relapse
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Drug therapy for recurrent prostate cancer
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Use of drug therapy for relapse
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The majority of prostate cancer patients who relapse go on to receive further antihormonal and