Pre- versus postoperative CAPOX plus bevacizumab (CAPOX-Bev) for resectable liver metastases from colorectal cancer (CLM): A randomized phase II/III trial (HiSCO-01).

Abstract

4021 Background: The role of neoadjuvant chemotherapy, particularly for those with initially resectable CLM, is controversial. And the optimal regimen and duration to be used in the neoadjuvant setting is not established. We conducted prospective, multicenter, randomized phase II/III study to assess pre-operative 8 cycles of CAPOX-Bev (arm A) plus radical surgery compared with post-operative 8 cycles of CAPOX-Bev (arm B) for patients (pts) with resectable CLM. Methods: The primary endpoint in the Phase II was completion rate of protocol treatment (more than 6 cycles of CAPOX-Bev plus R0 surgical resection) and PFS in the Phase III. The secondary endpoints were OS, ORR (arm A), liver damage (arm A), safety. The Phase III part was terminated due to slow enrollment. Results: 81 pts were enrolled from 10 centers between November 2010 and November 2017. The full analysis set consisted of 76 pts who started protocol treatment (arm A 37 vs. arm B 39). 76 pts had the following characteristics: median age 66 (27-80), median number of liver metastases 2 (1-14), 69.7% male, 67.1% synchronous and 94.7% primary resected. Completion rate of protocol treatment was 89.2% in arm A and 71.8% in arm B (p = .06). ORR was 63.9%, including 2 pts who had pathologically complete response (5.6%). Only 1 pts in arm A could not undergo surgery due to progression of disease. In the chemotherapy safety population, arm B was associated with more grade 3 neutropenia and grade 3 gastrointestinal disorder than arm A. The most frequent surgical adverse event was biliary fistula, with an incidence of 0% in arm A and 10.3% in arm B (p = .02). No patient died from treatment-related adverse events. The median follow-up time was 40 months. The rate of PFS at 3 years was 32.2% in arm A versus 38.5% in arm B (p = .99). Conclusions: Pre-operative 8 cycles of CAPOX-Bev is compatible with radical surgery, but may have no impact on progression-free survival compared with post-operative chemotherapy. Clinical trial information: UMIN000003783 .