Implications for Practice
cancer, tumors
CANCER, METASTATIC COLORECTAL CANCER, TUMORS
Epidermal growth factor receptor (EGFR) protein and the MAPK pathway (including the proteins RAS, RAF, MEK1/2, and ERK) are involved in cell growth and survival; activation of any of these proteins can cause cells to divide more rapidly, allowing cancer to develop. People with metastatic colorectal cancer (mCRC) tumors with activated RAS are resistant to anticancer medicines targeting EGFR due to activation of the MAPK pathway, limiting treatment options. Therefore, we used a combination of medicines. We tested panitumumab, which blocks EGFR, with binimetinib, which blocks MEK1/2, to see if resistance could be overcome. Adding binimetinib to panitumumab did not improve outcomes for people with mCRC with activated or nonactivated RAS regardless of a person’s previous history with EGFR blockers. In addition, many people found this combination of medicines hard to tolerate. This work showed that binimetinib plus panitumumab has limited benefit for people with activated or nonactivated RAS mCRC.