In June 2011, the European Medicines Agency (EMA) extended the licensed indication for panitumumab (Vectibix®), a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) to first- and second-line therapy in combination with chemotherapy in patients with non-mutated(wild-type, WT) KRAS (WT KRAS) metastatic colorectal cancer (mCRC).
Overall, two studies reporting results on panitumumab therapy in WT KRAS patients were identified. One study (PACCE) was halted after the first interim analysis based on inferior progression free survival (PFS) results and increased toxicity caused by the combination of two monoclonal antibodies. Even though the second trial (PRIME) could not show prolongation regarding overall survival, the PFS was statistically significantly longer when panitumumab was added to chemotherapy in WT KRAS patients compared to chemotherapy alone. As expected, adverse events were more frequent and more severe in the panitumumab arm, but were considered to be clinically manageable. Further, the PRIME trial confirmed that even though panitumumab targets the EGFR, KRAS status is currently the most important predictive factor for response to panitumumab.
Currently there are several different drugs and classes of drugs available for the treatment of mCRC. One of the future challenges will thus be to identify the optimal sequence, combination and duration of these drugs.