Yoshihiro Mise1, Kiyoshi Hasegawa2, Akio Saiura1, Masaru Oba3, Junji Yamamoto4, Yukihiro Nomura5, Tadatoshi Takayama6, Yojiro Hashiguchi7, Masayuki Shibasaki8, Hirohiko Sakamoto9, Seiichi Yamagata10, Nobuyoshi Aoyanagi11, Hironori Kaneko12, Hiroto Koyama13, Shinichi Miyagawa14, Eiji Shinozaki1, Shuntaro Yoshida3, Hiroaki Nozawa15, Norihiro Kokudo3. 1. Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto City, Japan. 2. Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan. kihase-tky@umin.ac.jp. 3. Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan. 4. National Defense Medical College, Tokorozawa, Japan. 5. Asahi General Hospital, Asahi, Japan. 6. Nihon University School of Medicine, Itabashi City, Japan. 7. Teikyo University School of Medicine, Itabashi City, Japan. 8. JCHO Tokyo Yamate Medical Center, Shinjuku City, Japan. 9. Saitama Cancer Center Hospital, Ina, Japan. 10. JCHO Tokyo Shinjuku Medical Center, Shinjuku City, Japan. 11. Kohnodai Hospital, National Center for Global-Health and Medicine, Shinjuku City, Japan. 12. Toho University Faculty of Medicine, Ota City, Japan. 13. JCHO Tokyo Takanawa Hospital, Minato City, Japan. 14. Shinshu University School of Medicine, Nagano, Japan. 15. Colon and Rectal Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Japan.
Abstract
BACKGROUND: The effect of cetuximab plus mFOLFOX on downsizing of the tumors for curative resection has yet to be assessed for patients with advanced colorectal liver metastases (CRLMs). This study aimed to assess the oncologic benefit of cetuximab plus mFOLFOX for wild-type KRAS patients with advanced CRLMs. METHODS: In this multicenter phase 2 trial, patients with technically unresectable tumor and/or five or more CRLMs harboring wild-type KRAS were treated with mFOLFOX plus cetuximab. The patients were assessed for resectability after 4 treatments, and then every 2 months up to 12 treatments. Patients with resectable disease were offered surgery after a waiting period of 1 month. The primary end point of the study was the R0 resection rate. The secondary end points were safety, progression-free survival (PFS), and overall survival (OS). The study is registered with the University Hospital Medical Information Network-Clinical Trials Registry Clinical Trials Registry (no. C000007923). RESULTS: Between 2012 and 2015, 50 patients from 13 centers were enrolled in this trial. Two patients were excluded because they had not received induction therapy. The 48 patients had a complete response rate of 0% and a partial response rate of 64.6%. For 26 R0 resections (54.2%) and 5 R1 resections (10.4%), no mortality occurred. During a median follow-up period of 31 months, the median OS for all the patients was calculated to be 41 months (95% confidence interval, 28-not reached). The 3-year OS rate was 59%. CONCLUSION: For patients with advanced CRLMs harboring wild-type KRAS, cetuximab administered in combination with mFOLFOX yields high response rates, leading to significantly high R0 resection rates and favorable prognoses.
BACKGROUND: The effect of cetuximab plus mFOLFOX on downsizing of the tumors for curative resection has yet to be assessed for patients with advanced colorectal liver metastases (CRLMs). This study aimed to assess the oncologic benefit of cetuximab plus mFOLFOX for wild-type KRASpatients with advanced CRLMs. METHODS: In this multicenter phase 2 trial, patients with technically unresectable tumor and/or five or more CRLMs harboring wild-type KRAS were treated with mFOLFOX plus cetuximab. The patients were assessed for resectability after 4 treatments, and then every 2 months up to 12 treatments. Patients with resectable disease were offered surgery after a waiting period of 1 month. The primary end point of the study was the R0 resection rate. The secondary end points were safety, progression-free survival (PFS), and overall survival (OS). The study is registered with the University Hospital Medical Information Network-Clinical Trials Registry Clinical Trials Registry (no. C000007923). RESULTS: Between 2012 and 2015, 50 patients from 13 centers were enrolled in this trial. Two patients were excluded because they had not received induction therapy. The 48 patients had a complete response rate of 0% and a partial response rate of 64.6%. For 26 R0 resections (54.2%) and 5 R1 resections (10.4%), no mortality occurred. During a median follow-up period of 31 months, the median OS for all the patients was calculated to be 41 months (95% confidence interval, 28-not reached). The 3-year OS rate was 59%. CONCLUSION: For patients with advanced CRLMs harboring wild-type KRAS, cetuximab administered in combination with mFOLFOX yields high response rates, leading to significantly high R0 resection rates and favorable prognoses.
Authors: Lee S Schwartzberg; Fernando Rivera; Meinolf Karthaus; Gianpiero Fasola; Jean-Luc Canon; J Randolph Hecht; Hua Yu; Kelly S Oliner; William Y Go Journal: J Clin Oncol Date: 2014-03-31 Impact factor: 44.544
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Authors: G Folprecht; T Gruenberger; W Bechstein; H-R Raab; J Weitz; F Lordick; J T Hartmann; J Stoehlmacher-Williams; H Lang; T Trarbach; T Liersch; D Ockert; D Jaeger; U Steger; T Suedhoff; A Rentsch; C-H Köhne Journal: Ann Oncol Date: 2014-02-27 Impact factor: 32.976
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Authors: René Adam; Aimery De Gramont; Joan Figueras; Ashley Guthrie; Norihiro Kokudo; Francis Kunstlinger; Evelyne Loyer; Graeme Poston; Philippe Rougier; Laura Rubbia-Brandt; Alberto Sobrero; Josep Tabernero; Catherine Teh; Eric Van Cutsem Journal: Oncologist Date: 2012-09-07
Authors: Volker Heinemann; Ludwig Fischer von Weikersthal; Thomas Decker; Alexander Kiani; Ursula Vehling-Kaiser; Salah-Eddin Al-Batran; Tobias Heintges; Christian Lerchenmüller; Christoph Kahl; Gernot Seipelt; Frank Kullmann; Martina Stauch; Werner Scheithauer; Jörg Hielscher; Michael Scholz; Sebastian Müller; Hartmut Link; Norbert Niederle; Andreas Rost; Heinz-Gert Höffkes; Markus Moehler; Reinhard U Lindig; Dominik P Modest; Lisa Rossius; Thomas Kirchner; Andreas Jung; Sebastian Stintzing Journal: Lancet Oncol Date: 2014-07-31 Impact factor: 41.316