Huabin Hu1,2, Kun Wang3, Meijin Huang4,2, Liang Kang4,2, Wei Wang5, Hui Wang4,2, Meng Qiu6, Rongbo Lin7,8, Haibo Zhang9,10, Ping Lan4,2, Xiaojian Wu4,2, Guangjian Liu11, Yunle Wan12, Ming Liu3, Zhiyang Zhou13, Yan Huang14, Fangqian Li13, Jianwei Zhang1,2, Yue Cai1,2, Tenghui Ma4,2, Jiaming Zhou4,2, Huaiming Wang4,2, Jiayu Ling1,2, Yonghua Cai4,2, Zehua Wu1,2, Shuangling Luo4,2, Li Ling15,16, Yanhong Deng1,2. 1. Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. 2. Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China. 3. Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China. 4. Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. 5. Department of Gastrointestinal Oncology, The First People's Hospital of Foshan, Foshan, People's Republic of China. 6. Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China. 7. Department of Gastrointestinal Oncology, Fujian Cancer Hospital, Fuzhou, People's Republic of China. 8. Fujian Medical University Cancer Hospital, Fuzhou, People's Republic of China. 9. Department of Oncology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People's Republic of China. 10. The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China. 11. Department of Medical Ultrasonics, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. 12. Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. 13. Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. 14. Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. 15. Sun Yat-sen Center for Migrant Health Policy, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China. 16. Faculty of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
Abstract
PURPOSE: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type. PATIENTS AND METHODS: Patients were enrolled to receive cetuximab (500 mg/m2 ) plus mFOLFOXIRI (oxaliplatin 85 mg/m2 , irinotecan 165 mg/m2 , folinic acid 400 mg/m2 , 5-fluorouracil 2,800 mg/m2 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety. RESULTS: Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%-48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%-36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups. CONCLUSION: Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM. IMPLICATIONS FOR PRACTICE: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.
PURPOSE: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type. PATIENTS AND METHODS: Patients were enrolled to receive cetuximab (500 mg/m2 ) plus mFOLFOXIRI (oxaliplatin 85 mg/m2 , irinotecan 165 mg/m2 , folinic acid 400 mg/m2 , 5-fluorouracil 2,800 mg/m2 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety. RESULTS: Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%-48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%-36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups. CONCLUSION: Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM. IMPLICATIONS FOR PRACTICE: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.
Authors: T Yoshino; D Arnold; H Taniguchi; G Pentheroudakis; K Yamazaki; R-H Xu; T W Kim; F Ismail; I B Tan; K-H Yeh; A Grothey; S Zhang; J B Ahn; M Y Mastura; D Chong; L-T Chen; S Kopetz; T Eguchi-Nakajima; H Ebi; A Ohtsu; A Cervantes; K Muro; J Tabernero; H Minami; F Ciardiello; J-Y Douillard Journal: Ann Oncol Date: 2018-01-01 Impact factor: 32.976
Authors: L Fornaro; S Lonardi; G Masi; F Loupakis; F Bergamo; L Salvatore; C Cremolini; M Schirripa; C Vivaldi; G Aprile; A Zaniboni; S Bracarda; G Fontanini; E Sensi; C Lupi; M Morvillo; V Zagonel; A Falcone Journal: Ann Oncol Date: 2013-05-10 Impact factor: 32.976
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