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Robin M Ross, PharmD Medical Science Liasion

Colorectal Cancer and Gastrointestinal Stromal Tumor: Disease State Overview and New Treatment Approaches. Robin M Ross, PharmD Medical Science Liasion. Colorectal Cancer (CRC) Epidemiology. NCCN Colon Cancer: Version 1, 2013.

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Robin M Ross, PharmD Medical Science Liasion

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  1. Colorectal Cancer and Gastrointestinal Stromal Tumor: Disease State Overview and New Treatment Approaches Robin M Ross, PharmD Medical Science Liasion

  2. Colorectal Cancer (CRC) Epidemiology • NCCN Colon Cancer: Version 1, 2013. • American Cancer Society. http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf. Accessed August 31, 2012. • American Cancer Society. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-028323.pdf. Accessed August 31, 2012. • National Cancer Institute. http://www.seer.cancer.gov/statfacts/html/colorect.html. Accessed August 31, 2012. • CRC is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the US1 • 143,460 new cases of CRC are estimated for 20122 • ~72% of cases arise in the colon and ~28% arise in the rectum3 • CRC incidence rate is more than 15x higher in adults aged ≥50 than in adults aged 20-493 • ~20% of patients have metastatic CRC (mCRC) when first diagnosed4 2

  3. Not all cases of CRC present with symptoms1 However, a variety of clinical symptoms can be associated with CRC1,2 Systemic Local Peritonitis Fatigue Anemia Ulcerations Palpitations Changed bowel habits Decreased appetite Abdominal pain and distension Weight loss Pale skin Rectal tenesmus Mucus and blood in stools Deep vein thrombosis Melena Signs and Symptoms of CRC • Abeloff. 2008. • DeVita. 2011. 3

  4. Screening for CRC • Goals of screening are to detect cancer at an early, curable stage, and to detect and remove adenomatous polyps1 • National Comprehensive Cancer Network (NCCN) guidelines recommend screening based on one’s risk status1 • The following are applicable to asymptomatic adults ≥50 of age2 • Although the US Preventive Services Task Force (USPSTF) recommends screening for people aged 50-75, it does not recommend screening for adults >753 • NCCN Colorectal Cancer Screening: Version 1, 2013. • Levin B, et al. CA Cancer J Clin. 2008;58:130-160. • US Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf08/colocancer/colcancs.pdf. Accessed August 31, 2012. 4

  5. An accurate diagnosis depends on the implementation of a range of clinical evaluations:1,2 Complete personal and family history Physical examination Laboratory tests (including blood, liver, and kidney tests) Colonoscopy Computed tomography scan (for the detection of possible metastases) Diagnosing CRC • Abeloff. 2008. • DeVita. 2011. 5

  6. Staging CRC (1) • NCCN Colon Cancer: Version 1, 2013. • Abeloff. 2008. • DeVita. 2011. • Following a CRC diagnosis, a pathological review of an endoscopically removed biopsy sample can determine the stage of CRC, which measures the anatomic extent of disease1,2 • The American Joint Committee on Cancer/Tumor Node Metastasis (AJCC/TNM) system is the most prominent and highly regarded:3 6

  7. Staging CRC (2) 7 • DeVita. 2011.

  8. CRC Stage and Five-Year Survival 8 • Abeloff. 2008.

  9. Prognoses for Patients with mCRC Remain Poor Men Women • 5-year relative survival rate for patients with CRC was 67% for 1999-2006 • Localized: 90% • Regional: 70% • Distant: 12% • 5-year CRC-specific survival by stage and race/ethnicity, 1999-2006: • American Cancer Society. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-028323.pdf. Accessed August 31, 2012. 9

  10. CRC Risk Factors 10 • American Cancer Society. http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf. Accessed August 31, 2012.

  11. Biomarkers in CRC: Improving Outcomes • Biomarkers in CRC allow: • Identification of patients who will benefit most from a specific treatment • Improved outcomes • Sparing of needless treatment-related toxicity • Reduced costs • Prognostic biomarkers provide information about overall outcome • Predictive biomarkers give information about the effects of treatment 11 • Tejpar S, et al. Oncologist. 2010;15:390-404.

  12. Biomarkers in CRC: Current Status Prognostic Shortened survival or no value Predictive Negative outcome with anti-EGFR agents in mCRC Prognostic Poor prognosis Predictive Negative outcome with anti-EGFR agents in mCRC • Several candidate biomarkers have been identified: • KRAS mutation • BRAF mutation 12 • Tejpar S, et al. Oncologist. 2010;15:390-404.

  13. KRAS Mutations in CRC • Present in 35-45% of CRC1 • May be associated with shortened survival1 • Predictive marker of response to EGFR therapy in CRC:1 • Only patients with wild-type KRAS benefit from cetuximab/panitumumab • Patients should be screened for KRAS status at the time of diagnosis of stage IV disease, prior to treatment2 • Tejpar S, et al. Oncologist. 201;15:390-404. • NCCN Colon Cancer: Version 1, 2013. 13

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