This patient did not undergo portal vein embolisation prior to hepatectomy. The hepatectomy did include segment IV.

The use of both FOLFOX (MOSAIC, Andre, et al. JCO 2009) and XELOX (NO16968, Haller, et al. JCO 2011) have been shown to significantly extend disease-free survival (DFS) and overall survival (OS) compared with 5-FU/LV alone in patients with stage III disease undergoing CRC surgery (final OS data not yet reported for NO16968). Bevacizumab plus FOLFOX showed a small, non-significant increase in DFS in C-08 (stage II/III) [Allegra, et al. JCO 2011; Allegra, et al. ASCO 2011 (abstract 3508)], suggesting that the addition of bevacizumab to chemotherapy after surgery when there is no evidence of disease may not increase survival benefit (data not available when this patient was treated).
However, in stage II/III disease the majority of patients experience a long period of DFS post-surgery, whereas in the metastatic setting patients are at a much greater risk of disease recurrence. Therefore, additional information is needed from randomised trials to determine whether it is appropriate to continue bevacizumab treatment after surgery for metastatic disease. Consequently, it is necessary to assess each patient individually, in this case, as treatment with bevacizumab plus FOLFOX was effective and well tolerated, it was decided to continue for a further 3 months (6 cycles) even though R0 resection was achieved.

Yes, there is clear evidence that bevacizumab provides therapeutic benefit in patients with mCRC and KRAS mutant status. A retrospective analysis of the AVF2107g trial [Hurwitz, et al. Oncologist 2009] demonstrated that KRAS mutant patients experienced a significant PFS benefit (9.3 months for chemotherapy plus bevacizumab versus 5.5 months for chemotherapy alone). Analyses of several other studies, including CAIRO-2, PACCE and AGITG MAX [Tol, et al. NEJM 2009; Hecht, et al. JCO 2009; Price, et al. JCO 2009], have also shown that bevacizumab appears to be effective in KRAS wild-type and mutant patients.

I think that it is, yes, as long as the known potential effects of bevacizumab on wound healing are taken into account. This means that bevacizumab should be withdrawn 5–6 weeks before elective surgery and not reintroduced for 4–5 weeks post-surgery, or until the wound is fully healed [Gruenberger, et al. JCO 2008; Avastin SmPC]. With regards to efficacy, bevacizumab appears to allow surgery in patients with potentially resectable liver metastases based on data showing response rates of greater than 70% and R0 resection in up to 40% of patients [Gruenberger, et al. JCO 2008, Wong, et al. Ann Oncol 2011, Doi, et al. Jpn J Clin Oncol 2010].

Usually I have no major preference for either regimen, bevacizumab has been demonstrated to be effective when combined with either FOLFOX or FOLFIRI in the non-randomised, observational studies BRiTE, First-BEAT and ARIES [Kozloff, et al. Oncologist 2009; Van Cutsem, et al. Ann Oncol 2009; Bendell, et al. ASCO GI 2011]. However, when the considering treatment of a patient with liver metastases post-surgery, I prefer FOLFOX as I feel that FOLFIRI is less effective for the management of microscopic disease. If the patient is unlikely to be a candidate for resection, I would use either regimen and, if the patient will never become resectable, I would actually choose FOLFIRI.

This is a very open question and really depends on when the disease returns and to which site. For example, in this case the patient is KRAS mutant and therefore not a candidate for an EGFR inhibitor. So, if the disease returned with visible lesions in the liver 1 year or more after resection, I would be comfortable to use bevacizumab with either FOLFOX or FOLFIRI. If the disease returned earlier, maybe less than 6 months after resection, I would change the chemotherapy backbone to FOLFIRI and reintroduce bevacizumab.