Treatment Sequencing in Metastatic Colorectal Cancer

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Multiple chemotherapeutic and biologic treatment approaches are feasible in the front-line management of patients with metastatic unresectable colorectal cancer (CRC). Until data supports a single best approach, the treatment decision relies heavily on preference.

The traditional front-line treatment for metastatic CRC is FOLFOX plus bevacizumab, Johanna Bendell, MD, notes. In some cases, bevacizumab will be administered with FOLFIRI and, in patients with KRAS mutations, FOLFIRI is combined with cetuximab, She explains. In general, without much data, treatment decisions should be tailored on an individual basis.

Following the advent of biologic agents, new considerations have arisen over potential interactions between biologics and chemotherapies. Axel Grothey, MD, explains that data supports a detrimental interaction between EGFR inhibitors and capecitabine or 5-FU. Several factors contribute to treatment interactions and inconsistent clinical trial data, Heinz-Josef Lenz, MD, explains. For instance, the administration route for 5-FU impacts the mechanism of action and the potential for interactions with other agents. Moreover, Lenz adds, the sequence order is an important factor, since each treatment changes the cancer cell composition.

In the search for ways to predict outcomes, moderator John L. Marshall, MD, offers the potential to incorporate vitamin D as a marker, since patients with less sun exposure seem to perform worse. However, Grothey notes, data seem consistent, regardless of sun exposure. As a result, he believes that administering all available treatments for longer durations is a better approach.

Further exploring the conversation on sequencing, Marshall mentions emerging data on maintenance therapy. Claus-Henning Köhne, MD, PhD, believes the long-lasting neuropathy associated with oxaliplatin treatment has sparked interest in maintenance therapy, since this approach allows for certain agents to be dropped from the regimen, following a given period of time. In general, the first treatment to be stopped is oxaliplatin followed by 5-FU, after varying lengths of time. Eventually, Bendell notes, treatment with bevacizumab alone may be sufficient.

Grothey notes that regardless of the sequence used in the maintenance setting, it is important to discusses treatment goals upfront with patients. Overall, he feels, the optimal approach should use the least amount of treatment necessary to control the disease while minimizing toxicity and improving quality of life.