Dr. Venook on Distinguishing Molecular Features in CRC

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 evolving treatment strategies for patients with colorectal cancer (CRC), with regards to molecular features such as sidedness.

Soon, physicians will be making treatment decisions less on mutational status, such as RAS, and more so on other factors, Venook explains. The most disappointing findings related to KRAS, as seen in the CALGB/SWOG 80405 study, are that patients did not perform better with cetuximab (Erbitux) even if they were KRAS-positive. Additionally, results showed that patients with right-sided tumors did not benefit from treatment with cetuximab. Hopefully, final data will explain what molecular features in the colon are allowing this to happen, he adds.

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.

Venook hopes that researchers will have the opportunity in the next year or 2 to explain not only why patients with left- versus right-sided tumors have better outcomes with select agents, but also to prospecively understand why this occurs and, therefore, how patients should be treated. Biomarker decision-making is not done often in practice currently, and physicians should be using that to determine what treatments to use versus what not to use.

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