Dr. Alan P. Venook on Determining Frontline Treatment for mCRC

Alan P. Venook, MD, The Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discusses factors in determining first-line treatment for patients with metastatic colorectal cancer (mCRC).

A big factor in determining optimal first-line treatment is if the patient is potentially curable or not, says Venook. As opposed to most solid tumors, some patients with mCRC are curable, particularly those with liver metastasis. How aggressive the treatment is should depend on the goals of treatment, he says.

It is not completely clear what the ramifications of different treatment are at this time, says Venook. Different studies have shown different findings,

In the European FIRE-3 study, frontline cetuximab (Erbitux) plus FOLFIRI improved OS by 3.7 months versus bevacizumab plus FOLFIRI in patients with KRAS wild-type metastatic CRC. However, no advantage was observed with either the primary endpoint of objective response rate or the secondary endpoint of progression-free survival (PFS).

In the CALGB/SWOG 80405 trial, the median overall survival was nearly 14 months longer in patients with left-sided tumors, including a nearly 20-month survival advantage in patients receiving frontline cetuximab plus chemotherapy and an over 7-month survival benefit in patients receiving frontline bevacizumab plus chemotherapy.

However, in the new EPIC trial cetuximab did not add to FOLFOX chemotherapy.

One possible explanation is that there are molecular subtypes of CRC that are overrepresented on the right side versus the left side.