Stakeholder Insight: Prostate Cancer - Hormone-refractory patients still waiting for treatment breakthroughs

Published by: Datamonitor

Published: Dec. 12, 2007 - 249 Pages

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Oncology pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the prostate cancer market

Contributing experts

Related reports

Upcoming reports

CHAPTER 2 INTRODUCTION AND SCOPE

Introduction

Coverage of the Stakeholder Insight Survey

Disease definition and epidemiology

Patient segmentation

Drug therapy for prostate cancer

Recurrent prostate cancer

Hormone-refractory prostate cancer

Pipeline products for hormone-refractory prostate cancer

CHAPTER 3 COUNTRY TREATMENT TREES

Introduction

Country treatment trees

US

Japan

France

Germany

Italy

Spain

UK

CHAPTER 4 DISEASE DEFINITION AND EPIDEMIOLOGY

Definition of prostate cancer

Prostate cancer

The most common cancer type and second leading cause of cancer-related death in males

Histology

The majority of prostate tumors are adenocarcinomas

Risk factors

Older age

Race

Family history

Hormones

Dietary factors

Symptoms

Symptoms frequently occur only at an advanced stage of prostate cancer

Screening and diagnosis

Measurement of PSA has proved fairly useful in the detection of prostate cancer, however, several issues need to be resolved

A widespread screening program exists in the US...

...however, in Europe, results from the ERSPC trial are necessary before screening programs can be considered

Though PSA screening has been shown useful in Japan, the practice is not widespread

Staging

Prostate cancer is staged using the TNM system and a histologically-based Gleason score

Epidemiology of prostate cancer

Incidence of prostate cancer

Prostate cancer is a tumor associated with older men, therefore incidence is rising in line with the ageing population

Mortality from prostate cancer

Potentially asymptomatic disease and a high rate of fatality from co-morbidities mean mortality from prostate cancer is not especially high

Prevalence of prostate cancer

Prevalence is high given the tendency for early diagnosis and low mortality

CHAPTER 5 PATIENT SEGMENTATION

Introduction

Staging of prostate cancer

Staging at diagnosis

Around half of all prostate cancer cases are diagnosed at a localized stage

Staging at the time of survey

A greater proportion have advanced-stage prostate cancer if patients at the time of survey are examined

One-quarter of all prostate cancer patients have hormone-refractory disease

Differences in staging

Urologists encounter more early-stage patients, while medical oncologists typically treat advanced disease...

...however, the difference is minimal in Japan due to its structure of medical practice

CHAPTER 6 INITIAL DRUG THERAPY FOR PROSTATE CANCER

Introduction

Overview of initial therapy for prostate cancer

Localized prostate cancer patients can undergo watchful waiting or radical prostatectomy

Initial treatment of locally advanced and metastatic prostate cancer constitutes androgen deprivation therapy

Initial treatment of prostate cancer

Initial use of drug therapy

As expected, use of initial drug therapy increases with an advancing stage of prostate cancer

However, a higher than expected proportion of localized stage patients appear to receive drug therapy

A lower proportion than average of locally advanced and metastatic prostate cancer patients receive initial drug therapy in the US

Specific initial drug therapy of prostate cancer

Across all stages of prostate cancer

LHRH agonist monotherapy and total androgen blockade are the favored drug regimens used in the initial treatment of prostate cancer

Localized prostate cancer

LHRH agonist monotherapy is generally sufficient given that an aggressive approach is not needed while the tumor is localized...

...however, in Spain and Japan, total androgen blockade is the favored initial treatment approach for localized prostate cancer

Anti-androgen monotherapy is the third most frequently used drug regimen for localized tumors due to its lower efficacy than medical castration

Use of cytotoxics with or without antihormonal therapy is very low in the initial treatment of localized prostate cancer

Locally advanced prostate cancer

On average, similar trends are seen in the initial treatment of locally advanced prostate cancer as for localized

More locally advanced patients receive TAB than localized patients, at the expense of use of anti-androgen monotherapy

Use of cytotoxics with or without antihormonal therapy is still low

Advanced prostate cancer

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

More advanced disease which may require more aggressive treatment means the combination of cytotoxics and antihormonal therapy is the third preferred initial regimen

Use of cytotoxics in the initial treatment of prostate cancer is relatively high across all stages in Germany

LHRH agonist monotherapy

Use of anti-androgens to counter testosterone flare

Use of anti-androgens to prevent testosterone flare from LHRH agonists increases with a more advanced stage of prostate cancer

Use of temporary anti-androgen therapy is, surprisingly, lowest in the US and Germany, and highest in the UK

Use of specific LHRH agonists as monotherapy

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

Goserelin is the second preferred LHRH agonist monotherapy across all stages of prostate cancer

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

Anti-androgen monotherapy

Use of specific anti-androgens as monotherapy

Bicalutamide, in varying dosing formulations, is the leading anti-androgen for use as monotherapy across all stage of prostate cancer

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

Casodex is by far the preferred anti-androgen for use as monotherapy in each of the seven major pharmaceutical markets

Casodex 150mg has had a tumultuous regulatory pathway to date

The EPC trial showed that 150mg Casodex daily is suitable for treatment of locally advanced prostate cancer, but not localized disease

Casodex 150mg is still used in localized prostate cancer, according to surveyed physicians

In Japan, only 80mg Casodex is available, while in the US, only 50mg Casodex is available

In the EU, use of Casodex is more fragmented between the 50mg and 150mg formulations

Use of flutamide is highest in the US

Use of cyproterone and nilutamide are highest in the EU

Total androgen blockade

Use of specific total androgen blockade regimens

A combination of leuprolide and bicalutamide is the top TAB regimen across all stages of prostate cancer

No specific recommendations for TAB regimen are made, therefore the choice of agents is most likely due to physician preference or cost

In the US and Japan, the top three TAB regimens do not vary by stage, with the leading combination constituting leuprolide and bicalutamide

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

Use of specific formulations of LHRH agonists

Use of specific formulations as monotherapy or as part of combination regimens

On average across the seven major markets, the three-month depot version of leuprolide is the leading formulation of LHRH agonist

Three-month goserelin emerges as the second preferred formulation of LHRH agonist

Three-month formulations of LHRH agonist are deemed to offer the most convenience and flexibility to patients

In the US, use of alternative leuprolide formulations is favored

Triptorelin and buserelin formulations appear in the top three preferred LHRH agonist formulations only in four of the EU countries

CHAPTER 7 RECURRENT PROSTATE CANCER

Introduction

Overview of therapy for recurrent prostate cancer

Treatment of recurrent prostate cancer typically involves further lines of antihormonal therapy

Remission rates

Remission rates by stage of disease

Remission rates are surprisingly high in the more advanced stages of prostate cancer, indicating that systemic therapy may offer sufficient disease control

High use of TAB to treat localized disease in Japan may result in a significantly higher remission rate in these patients

Duration of remission

Duration of remission is longest in localized prostate cancer patients and shortest in advanced patients

A high proportion of localized patients are initially treated with drug therapy in Spain, thereby resulting in a higher duration of remission

Relapse rates

Patients who relapse following remission

As expected, relapse rates are highest among advanced prostate cancer patients and lowest in localized disease

Highest relapse rates in Spain, albeit for no apparent reason

Stage of disease present at relapse

Due to enhanced detection of rising PSA levels, relapsed disease can be identified while still at a localized stage

Hormone-refractory disease at relapse

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

Drug therapy for recurrent prostate cancer

Use of drug therapy for relapse

The majority of prostate cancer patients who relapse go on to receive further antihormonal and/or cytotoxic therapy

Surprisingly, drug therapy for relapsed disease is highest in the Japan and lowest in the US

Specific drug regimens used to treat recurrent prostate cancer

Drug therapy following LHRH agonist monotherapy

In accordance with treatment guidelines, the majority of patients receive TAB for relapsed disease after undergoing LHRH agonist monotherapy as initial therapy

Cytotoxic-based regimens are the second preference after LHRH agonist monotherapy, most likely for those patients with HRPC at relapse

Third choice varies between anti-androgen monotherapy or LHRH agonist monotherapy depending on the country

Drug therapy following anti-androgen monotherapy

TAB appears the favored regimen to follow initial anti-androgen monotherapy

On average, LHRH agonist monotherapy appears the second preferred treatment approach following initial anti-androgen monotherapy, although in some countries use is equivalent to that of cytotoxic-based regimens

The seven-market average dictates that cytotoxic-based regimens are the third preferred treatment option following initial anti-androgen monotherapy

Anti-androgen monotherapy in both the initial and second-line treatment settings has been clinically proven to offer few benefits

Drug therapy following total androgen blockade

Cytotoxic-based regimens are administered to the majority of patients who receive initial therapy with TAB

Continued TAB appears to be the second most popular approach following initial TAB therapy, possibly as part of an intermittent dosing regimen

On average, the third favored approach following initial TAB is LHRH agonist monotherapy, although significant differences occur between individual countries

Drug therapy following cytotoxic-based regimens with or without antihormonal therapy

Cytotoxic-based regimens are not typically used as initial therapy, therefore second-line treatment is highly fragmented between countries

CHAPTER 8 HORMONE-REFRACTORY PROSTATE CANCER

Introduction

Overview of therapy for hormone-refractory prostate cancer

Taxotere-based chemotherapy forms the first-line standard of care for HRPC patients

Bisphosphonates can be used to prevent the formation of bone metastases and to alleviate bone pain

Optimal second-line therapy for HRPC is yet to be defined

Progression to hormone-refractory prostate cancer

Patients who progress to hormone-refractory prostate cancer

Patients diagnosed with advanced prostate cancer are more likely to progress to HRPC than earlier-stage patients

Duration of antihormonal therapy prior to progression to HRPC

Localized patients undergo a longer duration of hormonal therapy prior to development of HRPC, while advanced patients progress more quickly

Drug therapy for hormone-refractory prostate cancer

Use of drug therapy for HRPC

Given the aggressive nature of HRPC, approximately three-quarters of patients receive drug therapy as treatment

Highest use of initial drug therapy for HRPC seen in Japan, lowest use seen in the US

First-line drug therapy

First-line drug regimens used to treat HRPC

Taxotere-based chemotherapy regimens are used heavily across all seven major pharmaceutical markets in the first-line treatment of HRPC

The leading seven-market first-line regimen is Taxotere and prednisone, which is expected given that this combination has regulatory approval for treatment of HRPC in the US and EU

Single-agent estramustine and single-agent Taxotere see equal use in the first-line treatment of HRPC when the seven-market average is examined despite a lack of robust supporting clinical data

Greater evidence exists supporting the first-line use of a Taxotere and estramustine combination in comparison to either agent as monotherapy

Use of secondary hormonal therapy as first-line treatment for HRPC may still be appropriate in those cases where androgen receptors are still active

Second-line drug therapy

Progression from first-line to second-line therapy

The majority of HRPC patients progress to second-line therapy, although variation is shown across the seven major markets

Second-line drug regimens used to treat HRPC

Use of Taxotere-based regimens is still high in the second-line treatment of HRPC, although mitoxantrone is also used frequently at this stage

The leading seven-market second-line regimens are single-agent mitoxantrone and a combination of Taxotere and prednisone, both administered to equal proportions of HRPC patients

Single-agent Taxotere is the third leading second-line regimen for the treatment of HRPC, most likely due to a lack of other approved agents

Use of single-agent estramustine is still high in the second-line treatment of HRPC in Japan, as well as in France, Italy and Spain

Continued use of a combination of Taxotere and estramustine is seen in the second-line treatment of HRPC in Japan

In Germany, a combination of vinorelbine and estramustine appears in the top three second-line regimens, most likely due to vinorelbine's milder toxicities

Secondary hormonal therapy is used in the second-line treatment of HRPC in Italy and the UK, which is somewhat surprising at this late stage

Key prescribing influences

Key prescribing influences for drug therapy of HRPC

The ability to improve overall survival, symptoms and quality of life are the leading two influences on prescribing for treatment of HRPC

The third leading prescribing influence concerns side-effect profiles, which is obviously of significance following improvements to survival and quality of life

The importance of remaining key prescribing influences vary depending on country-specific issues, with cost issues, method and frequency of administration and physician product familiarity more or less of similar weight

Relatively high importance of cost issues is expected in the more cost-conservative UK, but not in the US

Method of administration, frequency of dosing and physician product familiarity are all of similar relevance in each of the seven markets

Pharmaceutical company marketing and services appears to be the least important key prescribing influence across the seven major markets

CHAPTER 9 PIPELINE PRODUCTS FOR HORMONE-REFRACTORY PROSTATE CANCER

Introduction

Prostate cancer pipeline overview

Key pipeline product profiles

Abbott's Xinlay (atrasentan)

Spectrum Pharmaceuticals/GPC Biotech's Orplatna (satraplatin)

Dendreon's Provenge (sipuleucel-T)

Cell Genesys's GVAX

Novacea/Schering-Plough's Asentar (calcitriol, DN-101)

Northwest Biotherapeutics' DCVax-Prostate

Genentech/Roche's Avastin (bevacizumab)

Key attributes

Key attributes for HRPC pipeline products

As expected, the top desired attributes in a pipeline drug for HRPC is to prolong overall survival duration and improve quality of life

Superiority over the current first-line standard

Clinical improvements required for a pipeline drug to be used ahead of the current first-line standard, Taxotere plus prednisone

In order for a pipeline drug to be used in combination with Taxotere over the current first-line standard, relatively large improvements in clinical benefits would need to be shown

Acceptable price increase for a pipeline drug to be used in advance of the current first-line standard, Taxotere plus prednisone

Physicians speculate that payers are prepared to pay nearly 20% more for a pipeline drug if survival is increased, even at the expense of increased toxicity

Predicted performance of late-phase pipeline products

Pipeline drugs are predicted to have some advantages over the current standard

Taxotere-based regimens are ranked highest in terms of overall survival and symptom/quality of life improvements, which is expected given the solid clinical evidence available

In terms of side-effect profile, method of administration and frequency of dosing, pipeline products are all ranked ahead of the standard Taxotere-based regimen, which is ranked the lowest for each

Provenge is ranked highest in terms of side-effect profile

Xinlay is ranked highest in terms of method of administration and frequency of dosing

No difference is shown between pipeline products in terms of cost issues

Taxotere and Avastin are ranked higher in terms of pharmaceutical company services, most likely owing to the large and well-established nature of their manufacturers

Taxotere-based regimens and Avastin were ranked highest in terms of physician product/class familiarity, which is not surprising, given these two agents are formally approved for treatment of cancer

Brand mapping

Interpreting a brand map

The brand map confirms the observations made with respect to predicted performance of pipeline products for HRPC

APPENDIX A

Physician research methodology

Physician sample breakdown

US

Japan

France

Germany

Italy

Spain

UK

Supplementary data

Brand map interpretation

Key opinion leader interview transcripts

APPENDIX B

The survey questionnaire

1. Patient segmentation

2. Drug therapy for prostate cancer

3. Recurrent prostate cancer

4. Hormone-refractory prostate cancer

5. Pipeline drugs

APPENDIX C

Bibliography

List of Tables

List of Figures

List of abbreviations

About Datamonitor

About Datamonitor Healthcare

About the Oncology analysis team

Disclaimer

Abstract

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