NEXUS trial: a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant colorectal oligometastases
Shin Kobayashi,
Hideaki Bando,
Akinobu Taketomi,
Takeshi Takamoto,
Eiji Shinozaki,
Manabu Shiozawa,
Hiroki Hara,
Kentaro Yamazaki,
Koji Komori,
Nobuhisa Matsuhashi,
Takeshi Kato,
Yoshinori Kagawa,
Mitsuru Yokota,
Eiji Oki,
Keigo Komine,
Shinichiro Takahashi,
Masashi Wakabayashi,
Takayuki Yoshino
Affiliations
Shin Kobayashi
Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East
Hideaki Bando
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
Akinobu Taketomi
Department of Gastroenterological Surgery I, Hokkaido University Hospital
Takeshi Takamoto
Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital
Eiji Shinozaki
Gastrointestinal Oncology Department, The Cancer Institute Hospital of JFCR
Manabu Shiozawa
Department of Gastrointestinal Surgery, Kanagawa Cancer Center
Hiroki Hara
Gastroenterological Department, Saitama Cancer Center
Kentaro Yamazaki
Division of Gastrointestinal Oncology, Shizuoka Cancer Center
Koji Komori
Department of Gastroenterological Surgery Aichi Cancer Center Hospital
Nobuhisa Matsuhashi
Department of Gastroenterological Surgery, Pediatric Surgery, Gifu University Hospital
Takeshi Kato
Department of Surgery, National Hospital Organization Osaka National Hospital
Yoshinori Kagawa
Department of Gastroenterological Surgery, Osaka General Medical Center
Mitsuru Yokota
Department of General Surgery, Kurashiki Central Hospital
Eiji Oki
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
Keigo Komine
Department of Clinical Oncology, Tohoku University Hospital
Shinichiro Takahashi
Department of Gastroenterological Surgery, Tokai University School of Medicine
Masashi Wakabayashi
Division for the Promotion of Drug and Diagnostic Development, National Cancer Center Hospital East
Takayuki Yoshino
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
Abstract Background The optimal treatment strategy for resectable BRAF V600E mutant colorectal oligometastases (CRM) has not been established due to the rarity and rapid progression of the disease. Since the unresectable recurrence rate is high, development of novel perioperative therapies are warranted. On December 2020, the BEACON CRC triplet regimen of encorafenib, binimetinib, and cetuximab was approved for unresectable metastatic colorectal cancer in Japan. Methods The NEXUS trial is a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant CRM. The key inclusion criteria are as follows: histologically diagnosed with colorectal adeno/adenosquamous carcinoma; RAS wild-type and BRAF V600E mutation by tissue or blood; and previously untreated resectable distant metastases. The triplet regimen (encorafenib: 300 mg daily; binimetinib: 45 mg twice daily; cetuximab: 400 mg/m2, then 250 mg/m2 weekly, 28 days/cycle) is administered for 3 cycles each before and after curative resection. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate and the secondary end points are the PFS, disease-free survival, overall survival, and objective response rate. The sample size is 32 patients. Endpoints in the NEXUS trial as well as integrated analysis with the nationwide registry data will be considered for seeking regulatory approval for the perioperative use of the triplet regimen. Discussion The use of the triplet regimen in the perioperative period is expected to be safe and effective in patients with resectable BRAF V600E mutant CRM. Trial registration jRCT2031220025, April. 16, 2022.
