Treatment of Unresectable RAS Wild-type Metastatic CRC

Panelists Johanna Bendell, MD, Sarah Cannon; Marwan Fakih, MD, City of Hope;
Heinz-Josef Lenz, MD, USC; John L. Marshall, MD, Georgetown; Alan P. Venook, MD, UCSF
Published Online: Friday, April 11, 2014
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The frontline treatment of patients with unresectable metastatic colorectal cancer (CRC) has become more challenging as a result of recent studies focused on RAS mutations. Evidence from the FIRE-3 study and retrospective RAS analyses suggest that cetuximab could be superior to bevacizumab as a frontline therapy, notes Marwan Fakih, MD. As a result, the EGFR inhibitors have moved forward in the treatment paradigm for patients with wild-type RAS.

Studies suggest that survival is superior when patients receive at least one EGFR inhibitor compared with at least one angiogenesis inhibitor, Fakih states. As a result, EGFR inhibition should be administered upfront, in order to ensure that at least one of these therapies is administered, Fakih believes. 

Until conclusive evidence is presented that one therapy is more effective, Johanna Bendell, MD, says that she plans to continue the frontline administration of bevacizumab for patients with RAS wild-type metastatic CRC. This decision is based largely upon the comparison of side effects between the two drugs, with a particular emphasis on dermatological toxicity.

In an expanded RAS analysis of the FIRE-3 study, the overall survival advantage was 7.5 months in favor of cetuximab compared with bevacizumab. This benefit, in conjunction with other RAS-focused studies, warrants the consideration of cetuximab in the first-line setting, believes Heinz-Josef Lenz, MD. Overall, the efficacy and toxicity for each agent should be discussed with patients before a decision is made, Lenz notes. 

Alan P. Venook, MD, suggests that he doesn’t commonly use biologic agents in the frontline setting for patients with metastatic CRC. However, results from the CALGB/SWOG 80405 study may provide more details on an optimal frontline therapy between cetuximab and bevacizumab. The median survival appears extraordinarily long for patients in the study, based on the length of time that has lapsed while the data matures, Venook states.
View More From This Discussion
Episode 1 Introduction: Expanded RAS Testing in Colorectal Cancer
Episode 2 Optimizing Treatment With EGFR Inhibitors in CRC
Episode 3 Clinical Development of Cetuximab in mCRC
Episode 4 Upfront Bevacizumab and Cetuximab Compared in mCRC
Episode 5 Treatment of Unresectable RAS Wild-type Metastatic CRC
Episode 6 First- and Later-line Use of Panitumumab in mCRC
Episode 7 Considerations When Selecting an EGFR Inhibitor in mCRC
Episode 8 Role of the Multikinase Inhibitor Regorafenib in mCRC
Episode 9 Role of the VEGF Inhibitor Aflibercept in mCRC
Episode 10 New Therapies in Development for mCRC
Episode 11 Tumor Profiling in Patients With mCRC
Episode 12 Current Trends in the Treatment of CRC
Episode 13 First- and Second-Line Treatment of mCRC in Specific Populations
Episode 14 Third-Line Treatment Options for mCRC
Episode 15 Panitumumab, Regorafenib, and Ziv-aflibercept in mCRC
Episode 16 Final Thoughts on the Treatment of mCRC
Expert Panelists
Dr. John L. Marshall

John L. Marshall, MD

Professor, Chief, Division of Hematology/Oncology,
Georgetown University Hospital,
Associate Director, Clinical Research,
Lombardi Comprehensive Cancer Center,

Johanna Bendell, MD

Director, GI Oncology Research
Associate Director, Drug Development Unit
Sarah Cannon Research Institute
Nashville, Tennessee

Marwan G. Fakih, MD

Professor and director
Gastrointestinal Medical Oncology
City of Hope, Duarte, California

Heinz-Josef Lenz, MD

Co-Director, Colorectal Center and GI Oncology Program, USC Norris Comprehensive Cancer Center,
Los Angeles, California

Alan P. Venook, MD

The Madden Family Distinguished Professor of Medical Oncology and Translational Research, University of California, San Francisco, San Francisco, California
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