The extent of an advantage seen with systemic perioperative therapy remains unclear for patients with metastatic colorectal cancer (mCRC). FOLFOX is used based on data from the newly diagnosed patient population in post patients, Axel Grothey, MD, explains. Patients with a single small liver metastasis should be considered for postoperative chemotherapy with FOLFOX. For more extensive hepatic metastases, perioperative chemotherapy has demonstrated an improvement in survival of approximately 25% in a pooled analysis.

Twelve cycles has been the standard for postoperative chemotherapy, although this standard should become closer to 6 cycles in the future to avoid neuropathy, suggests Alan Venook, MD. With the reduction to 6 cycles of combination chemotherapy further emphasis is placed on the role of maintenance therapy. Following oxaliplatin-containing therapy, maintenance capecitabine and bevacizumab has demonstrated efficacy in the phase III CAIRO3 trial for patients who respond well to frontline therapy.

In the CAIRO3 trial, patients received maintenance therapy with capecitabine plus bevacizumab or observation following induction treatment with capecitabine, oxaliplatin, and bevacizumab (CAPOX-B). After 48 months, CAPOX-B was reintroduced in 60% of patients with observation compared with 47% with maintenance. Median time to second progression (PFS2) was 8.5 months with observation compared with 11.7 months with maintenance therapy (HR = 0.67; P < .0001).

An optimal treatment following progression on maintenance bevacizumab and capecitabine has not yet been identified, since long-term outcomes were unclear in the CAIRO3 trial, notes John Marshall, MD. Reintroduction of frontline therapy or utilization of a chemotherapy regimen, such as FOLFIRI, are potential options. Additionally, clinical trials should be offered, potentially exploring an immunotherapy, notes Marshall.