Does the Presence of an Intact Primary Increase the Risk of Non-Elective Colorectal Surgery in Patients Treated with Bevacizumab?

AIM: In patients with incurable metastatic colorectal cancer (mCRC), primary tumour resection is debated; however, patients with intact primaries may be at higher risk of complications requiring surgery when receiving treatment with bevacizumab. We estimated the risk of non-elective colorectal surgery in patients undergoing bevacizumab therapy for mCRC and evaluated the association between intact primary tumours and risk of non-elective surgery METHODS: We designed a population-based, retrospective cohort study using administrative and cancer registry data in Ontario, Canada. We included patients with mCRC who received bevacizumab from Jan.1, 2008-Dec.31, 2014. The primary outcome was non-elective colorectal surgery after initiating bevacizumab. We determined the cumulative incidence of non-elective colorectal surgery among patients with previously resected and unresected primaries, accounting for the competing risk of death. We explored the relationship between previous resection of the primary and need for non-elective surgery using a cause-specific hazards model, controlling for patient, tumour, and treatment factors.

RESULTS: We identified 1,840 (32.7 %) patients with intact primaries and 3,784 (67.3%) patients with prior resection. The cumulative incidence of non-elective surgery 1 year after initiating bevacizumab for all patients was 3.9% (95%CI: 3.4-4.5%). One-year cumulative incidence was higher in those with intact primaries vs. those with resected primaries (6.1% vs. 2.9%, p<0.0001). After adjustment, an intact primary remained strongly associated with non-elective colorectal surgery (HR = 2.89, 95% CI: 2.32-3.61, p<0.0001).

CONCLUSIONS: Bevacizumab is associated with a low but meaningful risk for serious gastrointestinal complications, necessitating vigilance, particularly among patients with an intact primary tumour.