Bifractionated CPT-11 with LV5FU2 Infusion (FOLFIRI-3) In Combination with Bevacizumab Followed by a Capecitabine and Bevacizumab Maintenance Therapy: A Phase II Study in First-Line Metastatic Colorectal Cancers

ABSTRACT Background Bevacizumab (Bev) with FOLFIRI or FOLFOX regimen is a standard of care in first-line metastatic colorectal cancers (mCRC). As second-line regimen after FOLFOX, FOLFIRI-3 has shown a significantly better PFS in comparison with other irinotecan-based regimen. We therefore evaluated the safety, efficacy and possible predictive factors for FOLFIRI-3 in combination with Bev as initial treatment for mCRC. Since fully validated biomarkers in mCRC are still lacking, we decided to assess the prognostic value of Angiopoietin-2 (Ang-2). Patients and methods We conducted a three-institution phase II trial of FOLFIRI-3 regimen (irinotecan 100mg/m2 before and after a 46-hour continuous infusion of fluorouracil (2400 mg/m2) with Bev (5mg/kg day 1) repeated every 2 weeks, as first-line treatment in mCRC. Induction treatment (FOLFIRI-3 and Bev) was administrated for 6 months, followed by a maintenance treatment including Bev (7.5 mg/kg day 1) and capecitabine (1000 mg/m2 day 1 to 14), repeated every 3 weeks. Plasma VEGF and serum Ang-2 were measured at baseline. The primary endpoint was ORR. Secondary endpoints were PFS, OS, and biologic analysis of potential predictive factors of response to treatment. Results 61 patients were enrolled for treatment. The ORR was 66.7% (95% CI, 55-79). SD in 25% of patients (DCR of 91.7%). PFS was 12 months (95% CI, 9-16) and OS was 33 months (95% CI, 19-44). A total of 41 patients entered the maintenance phase of the study. Bev/capecitabine maintenance therapy appeared as an appropriate and well-tolerated option. High pre-therapeutic serum Ang-2 level was identified as a potential biomarker correlated to worse outcomes in this cohort (median progression free survival of 14.7 months vs. 7.3 months, p  Conclusions As front-line regimen in mCRC, FOLFIRI-3/Bev regimen, followed by a capecitabine-based maintenance therapy, is effective and might be considered for future development particularly in patients treated by oxaliplatin in the adjuvant setting. Serum angiopoietin 2 is a promising biomarker to predict PFS and OS in mCRC patients treated with chemotherapy and bevacizumab. External validation is in course. Disclosure All authors have declared no conflicts of interest.