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.

Authors

null

Genki Watanabe

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Genki Watanabe , Yoshihiro Mise , Masaru Oba , Akio Saiura , Yosuke Inoue , Yu Takahashi , Yoji Kishi , Koichi Suyama , Tadatoshi Takayama , Tamaki Noie , Yujiro Nishioka , Nobuhisa Akamatsu , Junichi Arita , Norihiro Kokudo , Kiyoshi Hasegawa

Organizations

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, Department of HPB Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan, Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, Department of Surgery, National Defense Medical College, Tokorozawa, Japan, Department of Medical Clinical Oncology, Toranomon Hospital, Tokyo, Japan, Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan, Department of Surgery, NTT Medical Center Tokyo, Tokyo, Japan, The University of Tokyo, Tokyo, Japan, Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, National Center for Global Health and Medicine, Tokyo, Japan

Research Funding

No funding received

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.

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Abstract Details

Meeting

2022 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Track

Pancreatic Cancer,Hepatobiliary Cancer,Neuroendocrine/Carcinoid,Small Bowel Cancer

Sub Track

Therapeutics

Clinical Trial Registration Number

000009530

DOI

10.1200/JCO.2022.40.4_suppl.450

Abstract #

450

Poster Bd #

Online Only

Abstract Disclosures