Considerations When Selecting an EGFR Inhibitor in mCRC

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The ASPECCT trial evaluated the efficacy of the EGFR inhibitors cetuximab and panitumumab in patients with previously treated KRAS wild-type metastatic colorectal cancer (mCRC). The results of this trial showed equivalence in response rate, progression-free survival, overall survival, or incidence of rash between the two therapies, according to John L. Marshall, MD. Based on findings from this trial and the phase III PRIME trial, the FDA approved panitumumab in combination with chemotherapy as a frontline treatment for patients with KRAS wild-type mCRC in May 2014.

Based on the efficacy and adverse event profiles of cetuximab and panitumumab, Johanna Bendell, MD, and Alan P. Venook, MD, favor panitumumab, due to the increased risk of infusion reactions with cetuximab. Heinz-Josef Lenz, MD, prefers cetuximab; in his opinion, cetuximab has less toxicity, particularly gastrointestinal toxicity. Marwan G. Fakih, MD, notes that based on the ASPECCT data, the difference in incidence of rash is small, and prophylactic treatments, such as doxycycline, minocycline, or topical hydrocortisone, may reduce the incidence of rash with panitumumab.

Following progression on an EGFR inhibitor, the panelists advise against the administration of a different EGFR inhibitor. Rather than trying a different EGFR inhibitor, Fakih suggests that he would stop therapy for 6 months and then rechallenge using the same EGFR inhibitor. Studies that explored this strategy demonstrated a favorable response rate, suggesting that rechallenge may be a viable option for these patients, Fakih believes.

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