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Modified FOLFOXIRI With or Without Cetuximab as Conversion Therapy in Patients with RAS/BRAF Wild‐Type Unresectable Liver Metastases Colorectal Cancer: The FOCULM Multicenter Phase II Trial |
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| Authors: | Huabin Hu Kun Wang Meijin Huang Liang Kang Wei Wang Hui Wang Meng Qiu Rongbo Lin Haibo Zhang Ping Lan Xiaojian Wu Guangjian Liu Yunle Wan Ming Liu Zhiyang Zhou Yan Huang Fangqian Li Jianwei Zhang Yue Cai Tenghui Ma Jiaming Zhou Huaiming Wang Jiayu Ling Yonghua Cai Zehua Wu Shuangling Luo Li Ling Yanhong Deng |
| Institution: | 1. Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China Contributed equally.;2. 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 Contributed equally.;3. Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China Contributed equally.;4. Department of Gastrointestinal Oncology, The First People's Hospital of Foshan, Foshan, People's Republic of China;5. Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, 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 Fujian Medical University Cancer Hospital, Fuzhou, People's Republic of China;8. Department of Oncology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People's Republic of China The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China;9. Department of Medical Ultrasonics, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China;10. Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China;11. 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;12. Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China;13. Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China;14. Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, 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 Faculty of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China;16. Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China |
| Abstract: | PurposeThis 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 MethodsPatients 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.ResultsBetween 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.ConclusionAddition 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 PracticeThis 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. |
| Keywords: | Modified FOLFOXIRI Cetuximab Conversion therapy Colorectal cancer Liver metastasis |