Treatment of Metastatic Colorectal Cancer - Episode 3

EPOC Studies: Preoperative Treatments in CRC

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The new EPOC study examined perioperative treatment with chemotherapy plus or minus cetuximab for KRAS wild-type patients with resectable liver metastases from colorectal cancer (CRC), explains Tanios Bekaii-Saab, MD. This trial was built off data from the original EPOC study that was conducted in 2008, which compared chemotherapy followed by surgery to surgery alone.

In this study, treatment with chemotherapy both before and after surgery demonstrated an improvement in progression-free survival of 3 years. However, despite the statistical significance of these results they were not clinically significant. The new EPOC study represented a natural extension of the original study by adding an EGFR inhibitor to chemotherapy, Bekaii-Saab believes.

Patients in the new EPOC trial were required to be KRAS wild type, which usually indicates a response to cetuximab. However, following approximately 45% of expected events, a planned interim analysis determined the study should be halted due to futility, explains Bekaii-Saab. Overall, the study showed that the addition of cetuximab to chemotherapy is not beneficial for patients with resectable liver metastases and KRAS wild-type CRC.

The chemotherapy used in this trial was predominantly FOLFOX. In general, other studies have indicated that FOLFOX plus cetuximab is not efficacious, notes Bekaii-Saab. The lack of benefits in this study largely came following resection, believes Axel Grothey, MD. This lack of benefit was also seen in the N0147 study, which contained an adjuvant FOLFOX plus or minus cetuximab arm for patients with CRC.

Inversely, studies have shown that adding the EGFR inhibitor panitumumab to FOLFOX is beneficial. The exact reason for why one EGFR inhibitor works with FOLFOX when another does not remains unknown. Outside of inhibiting EGFR, panitumumab and cetuximab each have a unique mechanism of action that may elicit very different responses, notes Alan P. Venook, MD. Panitumumab mediates antibody-dependent cellular cytotoxicity and may have a more potent dosing strategy, believes Venook. This drug was developed later than cetuximab and focused on the occurrence of a skin rash as an indication that the agent was working in order to find the most optimal dose, Venook states.