A multicenter phase II trial to assess the efficacy and safety of bevacizumab plus mFOLFOX6 as induction chemotherapy toward R0 surgical resection in advanced colorectal liver metastases with mutant-type KRAS: NEXTO-mt trial.

Abstract

450 Background: The oncological benefit of bevacizumab plus mFOLFOX6 in advanced colorectal liver metastases (CRLMs) in terms of conversion to curative resection remains unknown. This multicenter phase II trial aimed to evaluate the efficacy and safety of bevacizumab plus mFOLFOX6 as induction chemotherapy for advanced CRLMs harboring mutant-type KRAS. Methods: Patients who had advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included in this study. The induction chemotherapy of bevacizumab plus mFOLFOX6 was administered and assessed for resectability every 4 cycles. If the unresectable CRLMs were converted to be resectable, liver resection was planned after a waiting period of 4–6 weeks and followed by postoperative chemotherapy up to 12 cycles. The primary endpoint was R0 resection rate. The secondary endpoints were safety, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). The trial was conducted following approval from the Institutional Ethics Review Board of all institutions and registered in the University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000009530). Results: Between February 2013 and December 2017, 29 patients from six centers were enrolled in this trial. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). No mortality after liver resection occurred. During the median follow-up of 30.7 months (range, 7.2–82.6 months), the median OS for the 29 patients was 49.1 months. The 3-year PFS and OS rates were 7.4%, and 64.4%, respectively. The 3-year RFS rate was 10.0% in 20 patients who achieved R0 or R1 resections. Conclusions: Bevacizumab plus mFOLFOX6 achieved a high R0 resection rate with a favorable survival for patients with advanced CRLMs harboring mutant-type KRAS. Clinical trial information: UMIN000009530.