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SUMMARY
Overview
Introduction
Globally, esophageal cancer is the ninth most common tumor type and seventh
leading cause of cancer-related death, however, its incidence fluctuates
widely depending on geographical area. While relatively uncommon in Western
countries, 50% of patients still present with locally advanced unresectable or
distant metastatic disease, where treatment is complicated and chances of a
cure are reduced.
Scope
- Current diagnosis and treatment of esophageal cancer, including treatment
regimens by stage and ongoing controversies
- Issues, unmet needs, and geographical variations in screening and
treatment strategies
- Examination of pipeline activity and potential future opportunities for
drug developers
- Stakeholder opinions and interview transcripts based on qualitative
interviews with key opinion leaders from the US and Europe
Report Highlights
As the incidence of esophageal cancer subtypes shift due to a changing
prevalence of risk factors including an increasing incidence of obesity and
gastroesophageal reflux disease, preventative strategies may take on a more
prominent role and existing treatment paradigms will need to evolve in order
to yield improved patient outcomes.
Given that the majority of esophageal cancer patients present with locally
advanced unresectable or distant metastatic disease, as reflected by poor
overall survival rates and disease prognosis, increased rates of earlier
diagnosis and greater research into more effective systemic therapies is
crucial.
Due to a relatively low incidence in the West, esophageal cancer has not been
the most commercially attractive indication for US and EU drug developers, as
evidenced by the lack of approved agents for its treatment. However, there are
numerous targeted therapies in Phase II trials, which show potential to
transform existing treatment paradigms.
Reasons to Purchase
- Identify the limitations of current therapy available to esophageal cancer
patients and the potential of future therapy
- Understand current epidemiological trends in esophageal cancer and ongoing
treatment controversies
- Assess the opportunities for innovative targeted therapies in esophageal
cancer, particularly in metastatic disease
TABLE OF CONTENTS
- ABOUT DATAMONITOR HEALTHCARE
- About the Oncology pharmaceutical analysis team
- Nish Saini - Lead Analyst, Oncology
- CHAPTER 1 EXECUTIVE SUMMARY
- Scope of analysis
- Datamonitor insight into the esophageal cancer market
- As the incidence of esophageal cancer subtypes shift due to a changing
prevalence of risk factors, preventative strategies may take on a more
prominent role and existing treatment paradigms will need to evolve in
order to yield improved patient outcomes
- Conflicting opinions regarding the use of neoadjuvant
chemoradiotherapy for locally advanced disease requires clarification,
potentially via the future use of genetic profiling
- Given that the majority of patients present with advanced disease,
reflected by poor overall survival rates and disease prognosis, increased
rates of earlier diagnosis and greater research into more effective
systemic therapies is crucial
- Due to its relatively low incidence in the West, esophageal cancer has
not been the most commercially attractive indication for US and European
drug developers, as evidenced by the lack of approved agents for its
treatment. However, there are numerous targeted therapies in Phase II
trials, which have the potential to transform existing treatment paradigms
- CHAPTER 2 DISEASE OVERVIEW
- Introduction
- Disease overview
- Esophageal cancer: a major source of cancer-related death
- Anatomy of the esophagus
- Esophageal cancer
- Definition
- Increasing number of distal esophageal tumors
- Pathology
- Predominance of histolological subtypes varies by geographical region
- Epidemiology
- Increasing rates of adenocarcinoma in the West drive an increasing
incidence of esophageal cancer across the seven major markets
- Mortality from esophageal cancer is high in comparison to its
incidence due to a typically advanced stage at diagnosis
- Risk factors
- Risk factors are better defined for squamous cell carcinoma than for
adenocarcinoma
- Genetic and environmental factors
- Precursor conditions
- Symptoms
- A lack of initial symptoms mean half of patients present with
advanced disease
- Screening
- Regular surveillance of patients with Barrett's esophagus is
recommended
- Diagnosis
- Endoscopy is used most frequently in the West to diagnose esophageal
cancer
- Staging
- Esophageal cancer has been pathologically staged since 2002
- Survival
- The high rate of advanced-stage diagnoses is reflected by relatively
poor survival rates
- Prognosis
- Stage of disease is the main prognostic indicator for esophageal
cancer
- Prevention
- For Barrett's esophagus, a variety of preventative measures exist to
halt progression to malignancy
- Weight reduction may form a viable preventative strategy for GERD,
and ultimately, esophageal cancer
- Chemoprevention of esophageal cancer may be possible using NSAIDs or
aspirin
- CHAPTER 3 CURRENT TREATMENT OPTIONS AND CONTROVERSIES
- Introduction
- Treatment guidelines
- US treatment guidelines
- US treatment guidelines for esophageal cancer focus on the use of
chemoradiotherapy for most patients
- European treatment guidelines
- European treatment guidelines focus on the use of chemoradiotherapy
when surgery is not a viable option
- Treatment of esophageal cancer in Japan
- Greater emphasis is placed on surgery in Japan for the treatment of
esophageal cancer
- Treatment of early-stage and locally advanced esophageal cancer
- Surgery
- Resection has the greatest utility in the treatment of early-stage
esophageal cancer patients
- Primary chemoradiotherapy for locally advanced disease
- Primary chemoradiotherapy may provide a cure for locally advanced
esophageal cancer patients
- Neoadjuvant therapy
- Neoadjuvant radiotherapy has been shown of little use in improving
either resectability or survival
- Neoadjuvant chemotherapy has demonstrated a survival advantage
without increasing postoperative complications
- Neoadjuvant chemoradiotherapy confers a high level of
treatment-related mortality
- Several Phase III studies are ongoing to further investigate the
utility of neoadjuvant therapy
- Adjuvant therapy
- Adjuvant radiotherapy may result in decreased survival in comparison
with surgery alone
- Adjuvant chemotherapy: some regimens have conferred a survival
benefit, however, this treatment modality has not been widely
investigated
- Adjuvant chemoradiotherapy is not associated with survival benefits
and has not been widely investigated
- Clinical trial activity investigating adjuvant therapy in esophageal
cancer is somewhat limited
- Surgery versus systemic therapy or combined modality treatment for
locally advanced disease
- Genetic testing may eventually resolve the issue of what constitutes
ideal treatment for individual esophageal cancer patients
- Treatment of advanced-stage and metastatic esophageal cancer
- Radiotherapy
- Primary radiotherapy is reserved for palliative purposes or for
those patients medically unfit to undergo chemotherapy
- Chemotherapy for advanced disease
- No standard chemotherapy regimen exists for advanced disease due to
a lack of large-scale, randomized clinical trial data
- Cisplatin forms the basis of chemotherapy for esophageal cancer,
given that its single-agent activity is higher than any other cytotoxic
tested to date
- Phase II studies have shown combination chemotherapy to confer
increased survival, albeit at the expense of increased toxicity and
morbidity
- The NCCN recommends 5-fluorouracil or cisplatin-based chemotherapy
for metastatic esophageal cancer, since no Phase III studies have been
completed for 15 years
- The ECF (epirubicin, cisplatin and 5-fluorouracil) regimen is used
as standard chemotherapy for metastatic disease in the UK
- Despite an urgent need for more definitive data, no Phase III
clinical trials are currently ongoing
- Photodynamic therapy
- Photodynamic therapy forms an alternative palliative treatment
option in advanced esophageal cancer
- Axcan Pharma's Photofrin is approved for the palliation of advanced
esophageal cancer
- Estimated treatment of esophageal cancer in the five major European
markets
- Estimated use of surgery
- Heavier reliance on potentially curative surgery at the earlier
stages of esophageal cancer
- Estimated use of chemotherapy
- Not surprisingly, a heavy reliance is placed upon a combination of
cisplatin and 5-fluorouracil in the first-line treatment of esophageal
cancer in the EU
- CHAPTER 4 UNMET NEEDS
- Introduction
- Unmet needs
- Improving prognosis of esophageal cancer
- 50% of patients present with advanced disease, therefore better or
facilitated techniques to increase earlier diagnosis are needed
- Improving patient lifestyle factors could prevent or delay the onset
of esophageal cancer
- Enhanced treatment options required across all stages of disease
- New and more effective systemic therapies for advanced disease are
required
- More effective neoadjuvant or adjuvant therapy for patients who
undergo surgery, to reduce relapse rates
- Adequate palliative treatment options for metastatic esophageal
cancer patients are still necessary
- Future treatment of esophageal cancer
- More large-scale, randomized clinical trials are necessary to define
optimal treatment strategies at all stages of esophageal cancer
- Espohageal cancer fails to generate significant commercial interest
- Summary of unmet needs
- CHAPTER 5 PIPELINE ANALYSIS
- The esophageal cancer pipeline
- Phase III pipeline
- Pfizer's Camptosar (irinotecan) - current off-label use may mean
that formal approval may not be sought
- Sanofi-Aventis's Eloxatin (oxaliplatin) - results from the REAL-2
trial and recent genericization in Europe may increase uptake
- Roche's Xeloda (capecitabine) - pharmacoeconomic issues may hinder
uptake
- Phase I/II pipeline
- Already proven a popular target in colorectal cancer, EGFR
inhibitors have shown some antitumor activity to date in early-phase
trials for esophageal cancer
- Inhibition of angiogenesis appears a successful strategy in
gastroesophageal junction cancer, however, ongoing trials need to focus
only on esopahgeal cancer patients
- Definitive conclusions regarding the full potential of targeted
therapies in esophageal cancer cannot be made yet.
- CHAPTER 6 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
- Disclaimer
- List of Tables
- Table 1: Crude incidence rates of esophageal cancer by gender per
100,000 in the seven major pharmaceutical markets, 2002
- Table 2: Estimated incidence of esophageal cancer in the seven major
pharmaceutical markets, 2001-15
- Table 3: Crude mortality rates of esophageal cancer by gender per
100,000 in the seven major pharmaceutical markets, 2002
- Table 4: Incidence and mortality from esophageal cancer in 2001 and
2015 across the seven major pharmaceutical markets
- Table 5: Comparison of mortality to incidence ratios for selected
tumor types in the US, 2001
- Table 6: Risk factors for the development of esophageal cancer
- Table 7: Common presenting symptoms of esophageal cancer
- Table 8: Surveillance guidelines for patients with Barrett's esophagus
- Table 9: TNM classification system for esophageal cancer
- Table 10: TNM staging system for esophageal cancer
- Table 11: Stage distribution and five-year survival rates for
esophageal cancer in the US
- Table 12: Five-year survival by stage of esophageal cancer
- Table 13: Esophageal cancer treatment guidelines in the US
- Table 14: Esophageal cancer treatment guidelines for recurrent disease
in the US
- Table 15: Esophageal cancer treatment guidelines in Europe
- Table 16: Extent of resection of esophageal cancer
- Table 17: Results from the RTOG 85-01 study
- Table 18: Results from the INT-0123/RTOG 94-05 study
- Table 19: Results from randomized clinical trials comparing
neoadjuvant radiotherapy with surgery alone in potentially resectable
esophageal cancer
- Table 20: Results from the INT-0113 study comparing neoadjuvant
chemotherapy with surgery alone
- Table 21: Results from the MRC study comparing neoadjuvant
chemotherapy with surgery alone
- Table 22: Results from a meta-analysis of 11 studies investigating
neoadjuvant therapy for esophageal cancer
- Table 23: Results from randomized clinical trials comparing
neoadjuvant chemoradiotherapy with surgery alone
- Table 24: Results from a randomized clinical trial comparing
neoadjuvant chemoradiotherapy with or without surgery
- Table 25: Results from a randomized clinical trial comparing adjuvant
radiotherapy with surgery alone
- Table 26: Results from the JCOG-9204 trial comparing adjuvant
chemotherapy with surgery alone
- Table 27: Results from a randomized clinical trial investigating
adjuvant chemoradiotherapy
- Table 28: Single-agent activity of cytotoxics in advanced esophageal
cancer
- Table 29: Results from Phase II studies investigating combination
chemotherapy regimens for advanced esophageal cancer
- Table 30: Results from a randomized trial comparing ECF with FAMTX in
advanced esophagogastric cancer
- Table 31: Results from a randomized trial comparing ECF with MCF in
advanced esophagogastric cancer
- Table 32: Survival results from the REAL-2 study
- Table 33: Toxicity from the REAL-2 study
- Table 34: Proportion of patients at each stage of esophageal cancer
who undergo surgery across the five EU markets, 2006
- Table 35: Proportion of patients at each stage of esophageal cancer
who receive chemotherapy across the five EU markets, 2006
- Table 36: Proportion of stage III/IV esophageal cancer patients who
receive multiple lines of chemotherapy across the five EU markets, 2006
- Table 37: Use of first-line chemotherapy regimens in esophageal cancer
across the five EU markets, 2006
- Table 38: Use of second-line chemotherapy regimens in esophageal
cancer across the five EU markets, 2006
- Table 39: Use of third-line chemotherapy regimens in esophageal cancer
across the five EU markets, 2006
- Table 40: Phase III esophageal cancer pipeline, 2007
- Table 41: Ongoing clinical trials investigating Camptosar for
resectable esophageal cancer, 2007
- Table 42: Ongoing clinical trials investigating Camptosar for
metastatic or unresectable esophageal cancer, 2007
- Table 43: Ongoing clinical trials investigating Eloxatin for
esophageal cancer, 2007
- Table 44: Ongoing clinical trials investigating Xeloda for esophageal
cancer, 2007
- Table 45: Phase II esophageal cancer pipeline (cytotoxics), 2007
- Table 46: Phase II esophageal cancer pipeline (targeted therapies and
miscellaneous), 2007
- Table 47: Phase I esophageal cancer pipeline, 2007
- List of Figures
- Figure 1: Anatomy of the esophagus
- Figure 2: Cross section of the esophagus
- Figure 3: Esophageal cancer belt
- Figure 4: Estimated incidence of esophageal cancer in the seven major
pharmaceutical markets, 2001-15
- Figure 5: Incidence and mortality from esophageal cancer in 2001 and
2015 across the seven major markets
- Figure 6: Use of chemotherapy regimens in the treatment of esophageal
cancer across the five EU markets, 2006
- Figure 7: Summary of unmet needs in the esophageal cancer market, 2007
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