This is a patient for whom I would use FOLFIRI and cetuximab to achieve resectable disease. If the patient experienced a response prior to surgery or achieved stable disease, I would treat postoperatively to complete 12 cycles altogether, including whatever was administered prior to surgery.

I would be more likely to switch to a different chemotherapy regimen and use FOLFOXIRI with this patient. Because the disease is KRAS wt and the patient needs a response, I would add bevacizumab. However, the use of FOLFIRI would still be part of the discussion, and I would even be comfortable using FOLFOX in this 60-year-old patient.

Although both FOLFOX/bevacizumab and FOLFIRI/bevacizumab are reasonable options in the setting of a greater than 12-month disease-free interval, FOLFIRI/bevacizumab is a reasonable option as first-line treatment and provides a therapy that is different from the adjuvant regimen.

I would treat with FOLFIRI/bevacizumab. In this situation, I generally do not offer further treatment postoperatively but would observe the patient. We do not have data indicating that FOLFIRI-based regimens help in the adjuvant setting. However, the patient received FOLFOX before, and that didn’t cure the disease.

My answer has changed since ASCO 2013. Before ASCO, I would have chosen FOLFIRI and an EGFR antibody. After the data from the new EPOC study were presented at ASCO 2013, I would not recommend an EGFR antibody in this setting because the study showed a detrimental effect if cetuximab was added to chemotherapy for patients with KRAS wt disease and operable liver metastases. So my choice in this scenario is FOLFIRI and bevacizumab.

If I see a response, the question of whether to offer postoperative therapy can be uncertain because we have some data on oxaliplatin-based therapy and irinotecan-based therapy but they’re not strong. Having said that, if I saw a strong response in these lesions I would even consider using FOLFIRI postoperatively, but I would not use bevacizumab postoperatively.

We would use FOLFOXIRI with bevacizumab for 3 months prior to surgery. I would continue treatment for 3 months postoperatively if a complete resection were achieved.

I don’t believe any particular regimen is much more effective if resection is the goal. However, in a patient with borderline resectable disease, the fluoropyrimidine options are not advisable. I would prefer to administer FOLFOXIRI or one of FOLFOX, CAPOX or FOLFIRI with the addition of a biologic agent.

Because we are going for a response and trying to achieve resectability, I would either use FOLFIRI with cetuximab or FOLFOXIRI. For a patient who had received 6 months of FOLFOX, I would make sure that liver damage is not a concern. That would argue against FOLFOXIRI because of the chemotherapy-associated steatohepatitis. Postoperatively I don’t tend to use adjuvant EGFR antibody therapy because the data are negative in terms of its benefit to patients. I tend to use a model of 3 months before and 3 months after as was used in the EORTC-40983 trial.