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New Developments in Advanced CRC:
Refining Personalized Therapy and the Emergence of Novel Agents
CME

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Educational Objectives
• Cite and apply existing principles for personalized care in metastatic colorectal cancer (CRC), including molecular testing, patient functional status, and potential for resection, among others
• Summarize recent safety and efficacy data on novel targeted agents in CRC, including multitargeted kinase inhibitors and anti-VEGF therapies

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Overview

Colorectal cancer (CRC) is the second most prevalent cancer worldwide, and the third most frequent cause of cancer-related death—responsible for almost 500,000 deaths every year.1 In its early stage, the disease is often curable with surgery,2 and the 5-year survival rate for patients diagnosed with CRC in the United States is 62%.1 However, for the 25% of patients who present with metastatic CRC, the 5-year survival rate plummets to less than 10%.1 Recent developments in understanding the molecular biology of CRC and the pathways involved in tumor progression have offered fresh insight into the management of metastatic disease. This improved understanding has further opened up the possibility of tailoring treatment to the individual tumor, through the use of targeted therapies. This activity examines current principles for personalized treatment approaches in metastatic CRC and provides a concise analysis of the latest data on novel targeted agents for patients with this disease.

Quality Care in Advanced CRC: Personalizing Treatment According to Patient and Tumor Factors

The management of advanced CRC has both increased in complexity and become associated with more profound clinical benefits for patients, largely because of the availability of active chemotherapy, targeted agents, and validated biomarkers.3-10 Current clinical practice recommendations indicate that multiple management strategies may be used to achieve the goal of offering quality care.11 Indeed, most data have confirmed the benefit of agent selection and sequencing using all effective strategies—oxaliplatin, irinotecan, fluoropyrimidines, bevacizumab, cetuximab, panitumumab, surgery for resection of metastases—in various combinations and in different treatment settings, based on patient and tumor characteristics.11-49

Patient characteristics—such as age, gender, presence of comorbid conditions, or overall performance status (PS)—should, of course, factor into treatment decisions.50 Assessing which patients will benefit from an intensive approach is important in determining the initial treatment strategy.50 For example, in patients who are fit and who present with good PS and relatively aggressive disease, a more intensive oxaliplatin or irinotecan platform represents a reasonable choice, with the addition of agents such as bevacizumab or cetuximab guided in part by KRAS status (Figure 1). Therapy may be selected according to treatment goals—whether the patient is eligible for palliative therapy only or potentially curative treatment in settings where resection of metastases is possible. To achieve these ends while improving patient outcomes and quality of life, several treatment modifications—including intermittent platinum dosing,12 maintenance therapy,15 treatment beyond progression with targeted therapy,42 and neoadjuvant strategies combining targeted and cytotoxic options25—have been tested and/or validated by researchers. In addition, several less intensive options have been considered in the upfront setting for use in elderly individuals or patients with poor PS—for example, fluoropyrimidine-bevacizumab combinations have been associated with clinical benefits in older populations.7

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Challenge Question

What statement accurately summarizes the NCCN recommendations regarding the use of biomarkers in metastatic CRC (as of August 2012)?

a.

b.

c.

d.

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References

  1. Gill S et al. Aliment Pharmacol Ther. 2003;18:683-692.
  2. Galal KM et al. Indian J Cancer. 2011;48:47-54.
  3. Kopetz S et al. J Clin Oncol. 2009;27:3677-3683.
  4. Kesmodel SB et al. J Clin Oncol. 2008;26:5254-5260.
  5. Gruenberger B et al. J Clin Oncol. 2008;26:1830-1835.
  6. Dy GK et al. Clin Colorectal Cancer. 2009;8:88-93.
  7. Tebutt NC et al. J Clin Oncol. 2010;28:3191-3198.
  8. Gnerlich JL et al. Ann Surg. 2009;250:96-102.
  9. Poultsides GA et al. J Clin Oncol. 2009;27:3379-3384.
  10. Sargent DJ et al. J Clin Oncol. 2009;27:1948-1955.
  11. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. Colon Cancer. V.1.2012. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed August 17, 2012.
  12. Tournigand C et al. J Clin Oncol. 2006;24:394-400.
  13. Grothey A et al. 45th Annual Meeting of the American Society of Clinical Oncology (ASCO 2008). Abstract 4010.
  14. Chibaudel B et al. J Clin Oncol. 2009;27:5727-5733.
  15. Tabernero J et al. ASCO 2010. Abstract 3501.
  16. http://clinicaltrials.gov/ct2/show/NCT00442637?term=CAIRO+3&rank=1. Accessed August 17, 2012.
  17. http://www.clinicaltrials.gov/ct2/show/study/NCT00265824. Accessed August 17, 2012.
  18. Tournigand C et al. J Clin Oncol. 2004;22:229-237.
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  22. Douillard Y et al. 15th Congress of the European CanCer Organisation and the 34th European Society for Medical Oncology Multidisciplinary Congress (ECCO ESMO 2009). Abstract 10LBA.
  23. Peeters M et al. ECCO ESCMO 2009. Abstract 14LBA.
  24. Siena S et al. ASCO-GI 2010. Abstract 283.
  25. Folprecht G et al. Lancet Oncol. 2010;11:38-47.
  26. Garrett CR et al. ASCO 2007. Abstract. 14018.
  27. Allegra CJ et al. J Clin Oncol. 2009;27:2091-2096.
  28. Tejpar S et al. ASCO 2011. Abstract 3511.
  29. Adam R et al. Ann Surg Oncol. 2001;8:347-353.
  30. Adam R et al. ASCO 2006. Abstract 3521.
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  33. Abdalla EK et al. Ann Surg. 2004;239:818-827.
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  36. Garufi C et al. Br J Cancer. 2010;103:1542-1547.
  37. Folprecht G et al. ASCO-GI 2009. Abstract 296.
  38. McCahill LE et al. ASCO 2010. Abstract 3527.
  39. Grothey A et al. J Clin Oncol. 2008;26:5326-5334.
  40. Sobrero AF et al. J Clin Oncol. 2008;26:2311-2319.
  41. Cunningham D et al. N Engl J Med. 2004;351:337-345.
  42. ML 18147 study press release.
    http://www.firstwordplus.com/Fws.do?articleid=800048C82DCE45C89FDB03007D132AC4. Accessed August 17, 2012.
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  44. http://clinicaltrials.gov/ct2/show/NCT00484939?term=NCT00484939&rank=1. Accessed August 17, 2012.
  45. Fornaro L et al. Crit Rev Oncol Hematol. 2010 Jul 7 [Epub ahead of print].
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  47. Giantonio BJ et al. ASCO 2005. Abstract 2.
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  52. National Cancer Institute. http://www.cancer.gov/cancertopics/druginfo/fda-ziv-aflibercept/. Accessed August 10, 2012.
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  54. Allegra CJ et al. J Clin Oncol. 2012;30(suppl):Abstract 3505.
  55. Venook AP. “Colorectal Discussion,” Gastrointestinal (Colorectal) Cancer. ASCO 2012. http://www.asco.org/ASCOv2/MultiMedia/Virtual%20Meeting. Accessed August 10, 2012.
  56. Grothey A et al. J Clin Oncol. 2012;30(suppl):Abstract TPS3634.
  57. Van Cutsem E et al. J Clin Oncol. 2012;30(suppl):Abstract 3502.
  58. Siu LL et al. J Clin Oncol. 2012;30(suppl):Abstract 3504.
  59. Garrett CR. “Colorectal Discussion,” Gastrointestinal (Colorectal) Cancer. ASCO 2012. http://www.asco.org/ASCOv2/MultiMedia/Virtual%20Meeting. Accessed August 10, 2012.
  60. Richardson PG et al. Expert Opin Drug Metab Toxicol. 2012;8:623-633.
  61. Bendell JC et al. J Clin Oncol. 2012;30(suppl):Abstract LBA3501.
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The materials presented here are used with the permission of the authors and/or other sources.
These materials do not necessarily reflect the views of PeerView Press or any of its supporters.

This activity is supported by an educational grant from Sanofi-aventis U.S., Inc. A SANOFI COMPANY and Regeneron Pharmaceuticals.

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New Developments in Advanced CRC: Refining Personalized Therapy and the Emergence of Novel Agents

Program Description & Educational Objectives

This activity will offer a brief overview of current principles of care in the metastatic CRC setting, followed by a review of novel therapies currently under investigation in advanced disease—including therapies with applications in pretreated patients. The relevant molecular pathways that are providing therapeutic targets will be outlined, and important safety and efficacy data with novel agents will be discussed, with a focus on the following: 1) the potential clinical role of newer anti-VEGF agents, such as aflibercept and ramucirumab; 2) an update on multitargeted kinase inhibitors, including regorafenib, as well as their potential clinical applications; and finally, 3) the latest data on Akt/PI3K inhibition (eg, perifosine) and other novel strategies being developed in metastatic CRC.

Upon completion of this activity, participants should be better able to:

  • Cite and apply existing principles for personalized care in metastatic colorectal cancer (CRC), including molecular testing, patient functional status, and potential for resection, among others
  • Summarize recent safety and efficacy data on novel targeted agents in CRC, including multitargeted kinase inhibitors and anti-VEGF therapies

Target Audience

This activity has been designed to meet the educational needs of oncologists active in the management of patients with advanced CRC.

Requirements for Successful Completion

In order to receive credit, participants must view the activity and complete the post-test and evaluation form. There are no pre-requisites and there is no fee to participate in this activity or to receive CME credit. Statements of Credit are awarded upon successful completion of the post-test and evaluation form.

Media: Internet
Release and Expiration Dates: October 02, 2012 - October 01, 2013
Time to Complete: 15 minutes

Faculty & Disclosure / Conflict of Interest Policy

In accordance with ACCME requirements, Penn State College of Medicine has a conflict of interest policy that requires faculty to disclose relevant financial relationships related to the content of their presentations/materials. Any potential conflicts are resolved so that presentations are evidence-based and scientifically balanced.

Medical Director

Carmine DeLuca
PVI, PeerView Institute for Medical Education

Carmine DeLuca currently has no financial interests/relationships or affiliations in relation to this activity.

Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.

Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.

Sponsorship, Credit & Support

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Penn State College of Medicine and PVI, PeerView Institute for Medical Education. Penn State College of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

The Penn State College of Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Information about CME credit for this activity is available by contacting Penn State at 717-531-6483 or ContinuingEd@hmc.psu.edu. Reference course # G5195-13-T.

This CME activity is jointly sponsored by Penn State College of Medicine and PVI, PeerView Institute for Medical Education.

This activity is supported by an educational grant from Sanofi-aventis U.S., Inc. A SANOFI COMPANYRegeneron Pharmaceuticals

Disclosure of Unlabeled Use

The faculty of this educational activity may include discussions of products or devices that are not currently labeled for use by the FDA. Faculty members have been advised to disclose to the audience any reference to an unlabeled or investigational use.

No endorsement of unapproved products or uses is made or implied by coverage of these products or uses in our reports. No responsibility is taken for errors or omissions in reports.

Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings.


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