Gastric Cancer. Introduction

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Gastric Cancer Introduction Despite advances in surgery and the use of multimodality therapy, survival outcomes remain poor for gastric cancer patients. There is an urgent need for more effective therapies to improve survival rates in patients presenting with both localized and advanced disease. The recent approval of Herceptin (trastuzumab; Roche/Chugai) may pave the way for the introduction of more novel drugs Scope Analysis of the gastric cancer market based on a survey of 180 oncologists and GI specialists, supported by interviews with key opinion leaders. Epidemiologic forecasts of the gastric cancer patient populations in the seven major pharmaceutical markets. In-depth analysis of treatment patterns, regimens prescribed and treatment outcomes for gastric cancer patients. Discussion of unmet needs and overview of late-stage pipeline drugs. Research and analysis highlights Despite a declining trend in incidence rates, the total incidence of gastric cancer in the seven major pharmaceutical markets is forecast to increase over the next decade, driven by the aging populations in these countries. The number of incident cases is forecast to reach over 250,000 cases by the end of 2020. Because most patients with localized gastric cancer suffer a recurrence, survival is modest for patients with resectable disease. The best outcomes are seen in Japan, where relapse rates are lower compared with the West. In unresectable gastric cancer, survival is very poor and metastatic patients rarely live for more than 11.5 years. There are currently five drugs in company-sponsored Phase III development for advanced gastric cancer, all of which are molecular targeted therapies. While the extent to which these agents will improve patient outcomes remains to be seen, physicians are generally optimistic about the incorporation of these drugs into treatment. Key reasons to purchase this research Understand prescribing trends in the gastric cancer market Examine unmet need within the gastric cancer market and identify opportunities for new product development Enhance commercial positioning by increasing understanding of current dynamics within the gastric cancer market

Table of Contents OVERVIEW o Catalyst o Summary EXECUTIVE SUMMARY o Scope of the analysis o Datamonitor insight into the gastric cancer market o Contributing experts o Related reports o Upcoming reports 1. INTRODUCTION AND SCOPE o Coverage of the Stakeholder Insight Survey Epidemiology Treatment options Treatment trends Key prescribing influences and brand assessment Improving treatment outcomes o Assumptions and caveats 2. COUNTRY TREATMENT TREES o Introduction to treatment trees o US o Japan o France o Germany

o Italy o Spain o UK 3. EPIDEMIOLOGY o Introduction and background o Key points o Disease definition and diagnosis criteria o Global variation and historical trends Contemporary trends o Risk factors Dietary Helicobacter pylori infection Tobacco smoking Family history o Epidemiologic forecasting of gastric cancer Sources of epidemiologic data o Description of methods Statistical analysis o Results Current incident cases and future trends of gastric cancer Segmentation of incident cases o Discussion US Japan Europe Strengths of Datamonitor s epidemiologic projections o Conclusions 4. PATIENT SEGMENTATION

o Staging of gastric cancer patients o Segmentation of the gastric cancer population o Gastric adenocarcinoma 5. TREATMENT OPTIONS AND TRENDS o Overview of gastric cancer treatment options Surgery has a central role in the management of localized gastric cancer, but controversy remains regarding the extent of surgery Neoadjuvant and adjuvant approaches are employed in localized disease, in an attempt to prevent recurrence The treatment of advanced disease is based on best supportive care (BSC) and palliative chemotherapy o Treatment trends in resectable gastric cancer Stage I gastric cancer Resectable Stage II gastric cancer Resectable Stage III gastric cancer o Treatment trends in unresectable gastric cancer Unresectable Stage II gastric cancer Unresectable Stage III gastric cancer Stage IV gastric cancer 6. PRESCRIBING INFLUENCES AND BRAND ASSESSMENT o Factors influencing prescribing decisions in gastric cancer Overall survival is the most important prescribing influence for gastric cancer o Physician perception of selected branded drugs used in the treatment of gastric cancer Physicians think highly of Taxotere in terms of its clinical efficacy and are familiar with its clinical profile

Xeloda scores highly in terms of convenience and physician familiarity Herceptin is perceived as an effective and safe, but costly drug 7. IMPROVING TREATMENT OUTCOMES o Treatment outcomes Resectable gastric cancer Unresectable gastric cancer o Unmet needs The treatment of localized disease needs to be refined More effective therapies are needed for the treatment of advanced disease Research efforts should be directed towards the development of predictive markers and molecular targeted therapy o New product development Selected drugs in company-sponsored Phase III development for gastric cancer Afinitor (everolimus; Novartis) Avastin (bevacizumab; Roche/Chugai) Erbitux (cetuximab; Bristol-Myers Squibb/ Eli Lilly/Merck KGaA) Tykerb/Tyverb (lapatinib; GlaxoSmithKline) Ramucirumab (Eli Lilly) Physician perception of pipeline drugs BIBLIOGRAPHY o Journal papers and books o Websites APPENDIX A o Physician research methodology

o Physician sample breakdown US Japan France Germany Italy Spain UK o Contributing experts APPENDIX B o Datamonitor consulting o Disclaimer TABLES o Table: Cancer registry data sources and the regions covered from the seven major pharmaceutical markets, published to o Table: Incident gastric cancer cases in the seven major pharmaceutical markets, 2020 o Table: Distribution of incident cases of gastric cancer by sex in the seven major o Table: Age-specific incident cases of gastric cancer in the seven major o Table: Stage-specific gastric cancer incident cases in the seven major o Table: Classification of Stage IV gastric cancer according to the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) Tumor, Node, Metastasis (TNM) system o Table: Drugs approved for the treatment of gastric cancer

o Table: Definition of terms used in the treatment of resectable gastric cancer o Table: Percentage of Stage I gastric cancer patients who are treated with neoadjuvant chemotherapy (CT) alone by neoadjuvant CT regimen in the seven major o Table: Percentage of Stage I gastric cancer patients who are treated with neoadjuvant chemoradiotherapy (CRT) alone by neoadjuvant CRT regimen in the seven major o Table: Percentage of Stage I gastric cancer patients who are treated with adjuvant chemotherapy (CT) alone by regimen in the seven major o Table: Percentage of Stage I gastric cancer patients who are treated with adjuvant chemoradiotherapy (CRT) alone by regimen in the seven major o Table: Percentage of Stage I gastric cancer patients who are treated with neoadjuvant chemotherapy (CT) in combination with any adjuvant therapy by neoadjuvant CT regimen in the seven major pharmaceutical markets, o Table: Percentage of Stage I gastric cancer patients who are treated with adjuvant chemotherapy (CT) in combination with any neoadjuvant therapy by adjuvant CT regimen in the seven major o Table: Percentage of Stage I gastric cancer patients who are treated with neoadjuvant chemoradiotherapy (CRT) in combination with any adjuvant therapy by neoadjuvant CRT regimen in the seven major pharmaceutical markets, o Table: Percentage of Stage I gastric cancer patients who are treated with adjuvant chemoradiotherapy (CRT) in combination with any neoadjuvant therapy by adjuvant CRT regimen in the seven major pharmaceutical markets,

o Table: Percentage of resectable Stage II gastric cancer patients who are treated with neoadjuvant chemotherapy (CT) alone by regimen in the seven major o Table: Percentage of resectable Stage II gastric cancer patients who are treated with neoadjuvant chemoradiotherapy (CRT) alone by regimen in the seven major o Table: Percentage of resectable Stage II gastric cancer patients who are treated with adjuvant chemotherapy (CT) alone by regimen in the seven major o Table: Percentage of resectable Stage II gastric cancer patients who are treated with adjuvant chemoradiotherapy (CRT) alone by regimen in the seven major o Table: Percentage of resectable Stage II gastric cancer patients who are treated with neoadjuvant chemotherapy (CT) in combination with any adjuvant therapy by neoadjuvant CT regimen in the seven major o Table: Percentage of resectable Stage II gastric cancer patients who are treated with adjuvant chemotherapy (CT) in combination with any neoadjuvant therapy by adjuvant CT regimen in the seven major o Table: Percentage of resectable Stage II gastric cancer patients who are treated with neoadjuvant chemoradiotherapy (CRT) in combination with any adjuvant therapy by neoadjuvant CRT regimen in the seven major o Table: Percentage of resectable Stage II gastric cancer patients who are treated with adjuvant chemoradiotherapy (CRT) in combination with any neoadjuvant therapy by adjuvant CRT regimen in the seven major o Table: Percentage of resectable Stage III gastric cancer patients who are treated with neoadjuvant chemotherapy (CT) alone by regimen in the seven major

o Table: Percentage of resectable Stage III gastric cancer patients who are treated with neoadjuvant chemoradiotherapy (CRT) alone by regimen in the seven major o Table: Percentage of resectable Stage III gastric cancer patients who are treated with adjuvant chemotherapy (CT) alone by regimen in the seven major o Table: Percentage of resectable Stage III gastric cancer patients who are treated with adjuvant chemoradiotherapy (CRT) alone by regimen in the seven major o Table: Percentage of resectable Stage III gastric cancer patients who are treated with neoadjuvant chemotherapy (CT) in combination with any adjuvant therapy by neoadjuvant CT regimen in the seven major o Table: Percentage of resectable Stage III gastric cancer patients who are treated with adjuvant chemotherapy (CT) in combination with any neoadjuvant therapy by adjuvant CT regimen in the seven major o Table: Percentage of resectable Stage III gastric cancer patients who are treated with neoadjuvant chemoradiotherapy (CRT) in combination with any adjuvant therapy receiving each by neoadjuvant CRT regimen in the seven major o Table: Percentage of resectable Stage III gastric cancer patients who are treated with adjuvant chemoradiotherapy (CRT) in combination with any neoadjuvant therapy by adjuvant CRT regimen in the seven major o Table: Percentage of unresectable Stage II gastric cancer patients who are treated with first-line chemotherapy (CT) by regimen in the seven major o Table: Percentage of unresectable Stage II gastric cancer patients who are treated with first-line chemoradiotherapy (CRT) by regimen in the seven major

o Table: Percentage of unresectable Stage III gastric cancer patients who are treated with first-line chemotherapy (CT) by regimen in the seven major o Table: Percentage of unresectable Stage III gastric cancer patients who are treated with first-line chemoradiotherapy (CRT) by regimen in the seven major o Table: Percentage of Stage IV gastric cancer patients who are treated with first-line chemotherapy (CT) by regimen in the seven major o Table: Percentage of Stage IV gastric cancer patients treated with secondline chemotherapy (CT) by regimen in the seven major pharmaceutical markets, o Table: Mean rating of selected branded drugs used in the treatment of gastric cancer (scale 1 10), indicating perceived performance, o Table: Drugs in company-sponsored Phase III development for gastric cancer, o Table: Afinitor (everolimus; Novartis) drug profile, o Table: Avastin (bevacizumab; Roche/Chugai) drug profile, o Table: Erbitux (cetuximab; Bristol-Myers Squibb/Eli Lilly/Merck KGaA drug profile, o Table: Tykerb (lapatinib; GlaxoSmithKline) drug profile, o Table: Ramucirumab (Eli Lilly) drug profile, o Table: Mean percentage of gastric cancer patients expected to receive regimens incorporating selected pipeline drugs in 5 years time, o Table: US physician sample breakdown, o Table: Japan physician sample breakdown, o Table: France physician sample breakdown, o Table: Germany physician sample breakdown, o Table: Italy physician sample breakdown, o Table: Spain physician sample breakdown, o Table: UK physician sample breakdown,

FIGURES o Figure: Treatment of Stage I gastric cancer patients in the US (1 of 2), o Figure: Treatment of Stage I gastric cancer patients in the US (2 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in the US (1 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in the US (2 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in the US (1 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in the US (2 of 2), o Figure: Treatment of unresectable Stage II gastric cancer patients in the US, o Figure: Treatment of unresectable Stage III gastric cancer patients in the US, o Figure: Treatment of Stage IV gastric cancer patients in the US, o Figure: Treatment of Stage I gastric cancer patients in Japan (1 of 2), o Figure: Treatment of Stage I gastric cancer patients in Japan (2 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in Japan (1 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in Japan (2 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in Japan (1 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in Japan (2 of 2), o Figure: Treatment of unresectable Stage II gastric cancer patients in Japan,

o Figure: Treatment of unresectable Stage III gastric cancer patients in Japan, o Figure: Treatment of Stage IV gastric cancer patients in Japan, o Figure: Treatment of Stage I gastric cancer patients in France (1 of 2), o Figure: Treatment of Stage I gastric cancer patients in France (2 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in France (1 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in France (2 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in France (1 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in France (2 of 2), o Figure: Treatment of unresectable Stage II gastric cancer patients in France, o Figure: Treatment of unresectable Stage III gastric cancer patients in France, o Figure: Treatment of Stage IV gastric cancer patients in France, o Figure: Treatment of Stage I gastric cancer patients in Germany (1 of 2), o Figure: Treatment of Stage I gastric cancer patients in Germany (2 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in Germany (1 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in Germany (2 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in Germany (1 of 2),

o Figure: Treatment of resectable Stage III gastric cancer patients in Germany (2 of 2), o Figure: Treatment of unresectable Stage II gastric cancer patients in Germany, o Figure: Treatment of unresectable Stage III gastric cancer patients in Germany, o Figure: Treatment of Stage IV gastric cancer patients in Germany, o Figure: Treatment of Stage I gastric cancer patients in Italy (1 of 2), o Figure: Treatment of Stage I gastric cancer patients in Italy (2 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in Italy (1 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in Italy (2 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in Italy (1 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in Italy (2 of 2), o Figure: Treatment of unresectable Stage II gastric cancer patients in Italy, o Figure: Treatment of unresectable Stage III gastric cancer patients in Italy, o Figure: Treatment of Stage IV gastric cancer patients in Italy, o Figure: Treatment of Stage I gastric cancer patients in Spain (1 of 2), o Figure: Treatment of Stage I gastric cancer patients in Spain (2 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in Spain (1 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in Spain (2 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in Spain (1 of 2),

o Figure: Treatment of resectable Stage III gastric cancer patients in Spain (2 of 2), o Figure: Treatment of unresectable Stage II gastric cancer patients in Spain, o Figure: Treatment of unresectable Stage III gastric cancer patients in Spain, o Figure: Treatment of Stage IV gastric cancer patients in Spain, o Figure: Treatment of Stage I gastric cancer patients in the UK (1 of 2), o Figure: Treatment of Stage I gastric cancer patients in the UK (2 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in the UK (1 of 2), o Figure: Treatment of resectable Stage II gastric cancer patients in the UK (2 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in the UK (1 of 2), o Figure: Treatment of resectable Stage III gastric cancer patients in the UK (2 of 2), o Figure: Treatment of unresectable Stage II gastric cancer patients in the UK, o Figure: Treatment of unresectable Stage III gastric cancer patients in the UK, o Figure: Treatment of Stage IV gastric cancer patients in the UK, o Figure: Age-adjusted gastric cancer incidence rates per 100,000 in the seven major pharmaceutical markets, 2008 o Figure: Historical age-adjusted incidence rates in men in the seven major pharmaceutical markets, 1983 2002 o Figure: Historical age-adjusted incidence rates in women in the seven major pharmaceutical markets, 1983 2002

o Figure: Percentage of Stage I gastric cancer patients receiving each type of therapy (neoadjuvant, adjuvant, both neoadjuvant and adjuvant) and surgery alone in the US, five major European markets (5EU) and Japan, o Figure: Percentage of Stage I gastric cancer patients receiving each type of neoadjuvant therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of Stage I gastric cancer patients receiving each type of adjuvant therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of Stage I gastric cancer patients receiving each type of perioperative therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of Stage II gastric cancer patients treated initially with surgery in the seven major o Figure: Percentage of resectable Stage II gastric cancer patients receiving each type of therapy (neoadjuvant, adjuvant, both neoadjuvant and adjuvant) and surgery alone in the US, five major European markets (5EU) and Japan, o Figure: Percentage of resectable Stage II gastric cancer patients receiving each type of neoadjuvant therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of resectable Stage II gastric cancer patients receiving each type of adjuvant therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of resectable Stage II gastric cancer patients receiving each type of perioperative therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of Stage III gastric cancer patients treated initially with surgery in the seven major

o Figure: Percentage of resectable Stage III gastric cancer patients receiving each type of therapy (neoadjuvant, adjuvant, both neoadjuvant and adjuvant) and surgery alone in the US, five major European markets (5EU) and Japan, o Figure: Percentage of resectable Stage III gastric cancer patients receiving each type of neoadjuvant therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of resectable Stage III gastric cancer patients receiving each type of adjuvant therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of resectable Stage III gastric cancer patients receiving each type of perioperative therapy in the US, five major European markets (5EU) and Japan, o Figure: Percentage of unresectable Stage II gastric cancer patients receiving chemotherapy, radiotherapy, chemoradiotherapy, and best supportive care as first-line treatment in the US, five major European markets (5EU) and Japan, o Figure: Percentage of unresectable Stage III gastric cancer patients receiving chemotherapy, radiotherapy, chemoradiotherapy, and best supportive care as first-line treatment in the US, five major European markets (5EU) and Japan, o Figure: Percentage of unresectable Stage III gastric cancer patients receiving 5-fluorouracil and Xeloda-based regimens as first-line therapies in the US, five major European markets (5EU) and Japan, o Figure: Percentage of Stage IV gastric cancer patients receiving chemotherapy, radiotherapy and best supportive care as first-line treatment in the US, five major European markets (5EU) and Japan, o Figure: Percentage of Stage IV gastric cancer patients receiving 5- fluorouracil- and Xeloda-based regimens as first-line therapies in the US, five major European markets (5EU) and Japan,

o Figure: HER2 status by stage of disease for gastric cancer patients who are tested for HER2 status in the seven major o Figure: Percentage of Stage IV gastric cancer patients receiving secondline chemotherapy (CT) in the seven major o Figure: Percentage of Stage IV gastric cancer patients treated with secondline chemotherapy (CT) who receive further lines of CT in the seven major o Figure: Mean points allocated to each drug attribute (out of 100 points), indicating their degree of influence on treatment decisions for gastric cancer, o Figure: Average percentage of Stage I gastric cancer patients who achieve remission/cure and average percentage of patients who, following remission/cure, suffer a relapse in the US, five major European markets (5EU) and Japan, o Figure: Average percentage of resectable Stage II gastric cancer patients who achieve remission/cure and average percentage of patients who, following remission/cure, suffer a relapse in the US, five major European markets (5EU) and Japan, o Figure: Average percentage of resectable Stage III gastric cancer patients who achieve remission/cure and average percentage of patients who, following remission/cure, suffer a relapse in the US, five major European markets (5EU) and Japan, o Figure: Average duration between curative treatment and relapse for Stage I, resectable Stage II and resectable Stage III gastric cancer in the seven major o Figure: Japan s percentage increase in the rate of remission/cure and percentage decrease in the rate of relapse compared with the corresponding US rates for Stage I, resectable Stage II and resectable Stage III gastric cancer, o Figure: Average survival time in months for Stage I gastric cancer patients who receive neoadjuvant and/or adjuvant therapy versus no therapy in

addition to surgery in the US, five major European markets (5EU) and Japan, o Figure: Average survival time in months for resectable Stage II gastric cancer patients who receive neoadjuvant and/or adjuvant therapy versus no therapy in addition to surgery in the US, five major European markets (5EU) and Japan, o Figure: Average survival time in months for resectable Stage III gastric cancer patients who receive neoadjuvant and/or adjuvant therapy versus no therapy in addition to surgery in the US, five major European markets (5EU) and Japan, o Figure: Japan s percentage increase in survival time compared with the US for Stage I, resectable Stage II, and resectable Stage III gastric cancer patients who receive neoadjuvant and/or adjuvant therapy, o Figure: Average survival time in months for unresectable Stage II gastric cancer patients who receive first-line therapy plus best supportive care (BSC) versus BSC alone in the US, five major European markets (5EU) and Japan, o Figure: Average survival time in months for unresectable Stage III gastric cancer patients who receive first-line therapy plus best supportive care (BSC) versus BSC alone in the US, five major European markets (5EU) and Japan, o Figure: Average survival time in months for unresectable Stage IV gastric cancer patients who receive first-line therapy plus best supportive care (BSC) versus BSC alone in the US, five major European markets (5EU) and Japan, o Figure: Mean ranking of each attribute for a pipeline drug for gastric cancer (scale 1 7), indicating their relative importance,