Market Report Source

Overview

Introduction
Cases of endometrial cancer are set to rise in developed countries due to an increase in risk factors such as obesity. In contrast, while incidence of cervical cancer is set to decrease in developed countries following the implementation of anti-HPV immunization with Merck & Co’s Gardasil and GlaxoSmithKline’s Cervarix, it will remain a major cause of cancer-related death in the developing world.

Scope
Current diagnosis and treatment of endometrial, cervical, vaginal and vulvar cancer, including treatment regimens by stage of disease
Issues and unmet needs in current treatment, screening and potential anti-HPV vaccination programs
Examination of pipeline activity and potential future opportunities for drug developers
Stakeholder opinions and interview transcripts based on qualitative interviews with five opinion leaders from the US and Europe

Highlights
The advent of anti-HPV vaccines capable of preventing cervical cancer, Merck & Co’s Gardasil and GlaxoSmithKline’s Cervarix, represent a major breakthrough, capable of significantly reducing the burden of disease. However, maximal impact will depend on the ease by which cash-strapped developing countries are able to gain access to these vaccines.

Despite being the most common of the gynecological malignancies, drug development for endometrial cancer is minimal. Given the high rate of early diagnosis and cure, the development of systemic therapies for metastatic disease has not been prioritized. This relatively inactive pipeline may become more of an issue as disease incidence increases.

While ample Phase I/II clinical trial data has been reported for the gynecological malignancies, only a small number of Phase III studies have been completed to corroborate earlier results. To fully define treatment strategies and provide solid evidence for clinical decision making, more large-scale, randomized clinical trials are necessary.

Reasons to Purchase
Identify the limitations of current therapy for gynecological cancer and the potential of future therapy
Understand current epidemiological trends in gynecological cancer and ongoing treatment controversies
Assess the opportunities for innovative targeted therapies in gynecological cancer, particularly in metastatic disease

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Oncology pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of analysis

Datamonitor insight into the gynecological cancers market

CHAPTER 2 DISEASE OVERVIEW

Introduction

Disease overview

The female reproductive system

Gynecological cancers

Definition

Endometrial cancer

Cervical cancer

Vaginal cancer

Vulvar cancer

Pathology and classification

Endometrial cancer: adenocarcinomas account for majority of incidence

Cervical cancer: squamous cell carcinoma is the most common pathology

Vaginal cancer: clear distinction between pathologies must be made

Vulvar cancer: any malignancy of the skin can occur here

Epidemiology

Incidence of gynecological tumors

Mortality from gynecological tumors

Risk factors

Endometrial cancer: genetic and environmental factors

Endometrial cancer: precursor conditions

Cervical cancer: genetic and environmental factors

Cervical cancer: precursor conditions

Risk factors for vaginal cancer

Risk factors for vulvar cancer

Symptoms

Endometrial cancer: abnormality of early signs means most cases are diagnosed rapidly

Cervical cancer: routine screening means any changes in the cervix are observed at an early stage

Vaginal cancer: most cases are diganosed at an early stage despite a lack of initial symptoms

Vulvar cancer: early symptoms are non-specific

Screening

Endometrial cancer: absence of screening programs is offset by a high rate of early patient presentation

Cervical cancer: widespread screening has significantly reduced mortality

Vaginal cancer: routine pelvic examinations can detect early cases

Vulvar cancer: routine pelvic examinations can detect early cases

Diagnosis

Endometrial cancer: dilation and curettage is the gold standard for diagnosis

Cervical cancer: following a Pap smear test, diagnosis can be made via biopsies

Vaginal cancer and vulvar cancer: colposcopy and biopsy are used to make diagnoses

Staging

Endometrial cancer: FIGO staging takes into account prognostic factors

Cervical cancer: staged clinically

Vaginal cancer: standard TNM and FIGO staging

Vulvar cancer: also surgically staged

Survival

Propensity for early diagnosis is reflected in encouraging five-year survival rates for most gynecological cancers

Prognosis

Prognosis of gynecological cancers depends primarily upon stage of disease and tumor characteristics

Prevention

Endometrial cancer: countering estrogen with progestin may aid prevention

Cervical cancer: prevention of HPV via vaccination will be key in prevention of tumors

Vaginal and vulvar cancer: prevention of HPV and regular screening should aid prevention of tumors

CHAPTER 3 CURRENT TREATMENT OPTIONS

Introduction

Endometrial cancer

Treatment guidelines

The NCCN has recommended treatment guidelines for endometrial cancer

Stage-specific treatment

Stage I endometrial cancer: surgery alone is normally sufficient

Stage II endometrial cancer: radical hysterectomy is the standard

Stage III endometrial cancer: adjuvant radiotherapy can be administered at this stage

Stage IV endometrial cancer: depending on disease characteristics, radiotherapy, chemotherapy and/or hormonal therapy can be administered

Recurrent endometrial cancer: radiotherapy or chemotherapy is the standard, depending on site of recurrence

Cervical cancer

Treatment guidelines

Stage-specific treatment

Stage 0 cervical cancer: limited uterus-preserving surgery has the greatest utility

Stage IA cervical cancer: surgery is the standard here, although options to preserve fertility in younger patients are available

Stage IB cervical cancer: adjuvant radiotherapy can be adminstered in high-risk cases

Stage IIA cervical cancer: adjuvant chemoradiotherapy has been shown to increase survival

Stage IIB cervical cancer: nearly all patients at this stage receive chemoradiotherapy

Stage III cervical cancer: primary chemoradiotherapy is the standard at this stage

Stage IVA cervical cancer: treatment is similar to that for stage III cervical cancer

Stage IVB cervical cancer: treatment serves only palliative purposes at this stage

Recurrent cervical cancer: depending on the site of recurrence, chemotherapy, radiotherapy or pelvic exenteration may be of use

Vaginal cancer

Treatment overview

Stage-specific treatment

Stage 0 vaginal cancer: limited surgery preserves the vagina

Stage I vaginal cancer: surgery is the standard, with adjuvant radiotherapy for those with high-risk features

Stage II vaginal cancer: radiotherapy is the standard at this stage

Stage III vaginal cancer: treatment is similar to that for stage II disease

Stage IV vaginal cancer: chemotherapy can be adminstered for palliation of symptoms

Recurrent vaginal cancer: depending on the site of recurrence, radiotherapy or pelvic exenteration may be suitable

Vulvar cancer

Treatment overview

Stage-specific treatment

Stage 0 vulvar cancer: minimally invasive surgery is preferred

Stage I vulvar cancer: surgery typically forms the main treatment modality

Stage II vulvar cancer: adjuvant radiotherapy is administered where high-risk features are present

Stage III vulvar cancer: neoadjuvant radiotherapy can be used in selected cases to downgrade bulky tumors

Stage IV vulvar cancer: neoadjuvant chemoradiotherapy may be of some utility at this stage

Recurrent vulvar cancer: a combination of surgery and radiotherapy can be employed, depending on the site of recurrence

CHAPTER 4 CURRENT TREATMENT REGIMENS AND CONTROVERSIES

Introduction

Endometrial cancer

Surgery

Surgery for staging is relatively standard…

…however controversy exists over value of l ymphadenectomy

Adjuvant therapy

Many early-stage patients receive adjuvant radiotherapy despite a lack of definitive evidence for its use and defined standard regimens

Adjuvant chemotherapy plus radiotherapy confers clinical benefit in advanced disease, although further investigation in randomized trials is necessary

Benefits of adjuvant chemotherapy over radiotherapy in stage III and IV disease come at the price of increased toxicity

Meta-analysis demonstrates adjuvant use of progestins provides no clinical benefit

Neoadjuvant therapy

Neoadjuvant radiotherapy generally reserved for stage II patients with a large amount of cervical involvement

Chemotherapy for advanced disease

Cisplatin and doxorubicin are considered the most active agents in endometrial cancer

The randomized GOG-107 initially demonstrated clinical benefit via a cisplatin and doxorubicin combination

Subsequent trials have shown utility of paclitaxel in endometrial cancer…

…however, dropping cisplatin for paclitaxel was not of clinical benefit

A platinum and doxorubicin combination with or without paclitaxel is the current standard for advanced or recurrent disease

Despite recommendations, no cytotoxic is formally approved specifically for endometrial cancer

Actual use of cytotoxics relies heavily upon the platinum agents

Hormonal therapy

Progestational agents can be used in the primary treatment of advanced disease where surgery is not an option

To date, combined chemotherapy and hormonal therapy has demonstrated little clinical value

Tamoxifen may be of use in some patients, although overall utility is limited

Other hormonal agents require further investigation

Actual use of hormonal therapy relies heavily upon single-agent medroxyprogesterone

Novel molecular targeted therapies

Further research is needed to determine the utility of targeted therapies in endometrial cancer

The future treatment of endometrial cancer

Results from the ongoing GOG-210 trial should help to identify optimal treatment regimens for individual patients

Cervical cancer

Surgery

The clinical staging used for cervical cancer is inferior in predicting extent of disease

Surgery and radiotherapy are equally effective as curative treatment modalities for early-stage disease

Pelvic exenteration may offer a cure for recurrent cervical cancer

Neoadjuvant therapy

Neoadjuvant chemoradiotherapy is only recommended for those patients with bulky early-stage tumors, although further research is necessary

Adjuvant therapy

Adjuvant radiotherapy is recommended for treatment of node-negative stage I and II patients with high-risk tumor characteristics

Adjuvant chemoradiotherapy is recommended for treatment of node-positive stage I and II patients

First-line chemoradiotherapy

Consistency of positive clinical trial data means first-line chemoradiotherapy is recommended for the treatment of stages IIB–IVA cervical cancer

Chemotherapy for advanced or recurrent disease

Cisplatin-based chemotherapy remains the standard of care for advanced and recurrent cervical cancer

Cisplatin is consistently the most active single agent

Combination regimens have shown marginal increases in efficacy

FDA and EMEA approval of GlaxoSmithKline’s Hycamtin (topotecan) in 2006 represented the first formal US and European approval of a cytotoxic agent for cervical cancer

A number of other new cytotoxics are under investigation in clinical trials

Actual use of cytotoxics shows an initial heavy reliance on cisplatin, which decreases as multiple lines of therapy are adminstered

Novel molecular targeted therapies

Further research is needed to determine the utility of targeted therapies in cervical cancer

Prevention of cervical cancer

Advent of anti-HPV vaccines will cause a great impact the cervical cancer market

CHAPTER 5 UNMET NEEDS

Introduction

Unmet needs

Reducing incidence of gynecological malignancies

Awareness must be raised with regards to potential for early diagnosis

Anti-HPV vaccines must be made available in developing countries to reduce worldwide incidence of cervical cancer

Altering patient lifestyle factors may reduce incidence of endometrial cancer

Improved treatment options

Less invasive surgery is required for early-stage tumors

Better systemic therapy is required for metastatic and recurrent disease

More large-scale, randomized clinical trials are necessary to define optimal treatment strategies across all gynecological malignancies

Despite being the most common gynecological malignancy, the endometrial cancer pipeline is relatively sparse

No sign of increasing activity in the cervical cancer pipeline

Summary of unmet needs

CHAPTER 6 PIPELINE ANALYSIS

Introduction

The endometrial cancer pipeline

Phase III development

Phase III pipeline for endometrial cancer is characterized by an absence of innovative targeted treatments

Phase I/II development

Future treatment is likely to depend on successfully incorporating innovative targeted therapies, although identification of optimal targets is required

Commonality of mutations to mTOR pathway in endometrial cancer means its inhibition is a rational treatment strategy

EGFR family inhibitors require further research in order to reach optimal response rates

VEGF levels are a potential indicator of more aggressive endometrial cancer

The cervical cancer pipeline

Phase III development

Eli Lilly’s Gemzar (gemcitabine) – a potential alternative treatment option?

Sanofi-Aventis’s Tirazone (tirapazamine) – a viable option for potentiating standard chemoradiotherapy?

Phase I/II development

Targeted therapies likely to play a large role in the future of cervical cancer

VEGF is expressed in greater levels in larger tumors, thereby implicating a more aggressive type of cervical cancer

Overexpression of EGFR is indicative of a worse prognosis, therefore its inhibition may eventually prove successful

Prevention of cervical cancer

Vaccination against HPV has the potential to significantly reduce incidence of cervical cancer

Merck & Co’s Gardasil – the first anti-HPV vaccine to reach the market

GlaxoSmithKline’s Cervarix – still awaiting large-scale clinical trial results

Which vaccine will enjoy greater commercial success?

The vaginal cancer and vulvar cancer pipelines

Phase I/II development

Low incidence has resulted in an empty pipeline

CHAPTER 7 KEY OPINION LEADER INTERVIEW TRANSCRIPTS

Contributing experts

Key opinion leader interview transcripts

APPENDIX

Bibliography

List of tables

List of figures

About Datamonitor

About Datamonitor Healthcare

About the Oncology analysis team

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