The fully human anti-
epidermal growth factor receptor (EGFR)
monoclonal antibody panitumumab has been shown to improve progression-free survival when administered as a monotherapy for patients with
chemotherapy-refractory metastatic
colorectal cancer (mCRC) and is approved in this setting. Two large randomized clinical trials have investigated
panitumumab in combination with
5-fluorouracil,
leucovorin, and
oxaliplatin (FOLFOX) as a first-line
therapy for mCRC and
5-fluorouracil,
leucovorin, and
irinotecan (FOLFIRI) as a second-line
therapy for mCRC. In these studies, the combination of
panitumumab with FOLFOX or FOLFIRI resulted in improved progression-free survival compared with FOLFOX or FOLFIRI alone. Improved
tumor response was also observed with the addition of
panitumumab to FOLFIRI. As in monotherapy trials, the clinical benefits associated with
panitumumab treatment were confined to patients with wild-type KRAS
tumors, further showing the validity of KRAS mutational status as a predictive
biomarker in mCRC. In addition to KRAS mutational status, a number of other potential predictive
biomarkers are currently being investigated in mCRC and may eventually help identify patients who are likely to benefit from treatment with anti-EGFR
monoclonal antibodies. Toxicities observed during treatment with
panitumumab combined with FOLFOX or FOLFIRI were generally manageable and commonly included skin toxicities and gastrointestinal toxicities. Because it can lead to dose delays,
dose reductions, and discontinuation, physicians and patients should carefully manage skin toxicity. Overall, the results of these two studies show that
panitumumab improves outcomes when added to FOLFOX or FOLFIRI among patients with mCRC with wild-type KRAS.