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

The oncologist

article

Huabin Hu¹  Ping Lan³  Xiaojian Wu³  Guangjian Liu⁴  Yunle Wan⁵  Ming Liu⁶  Zhiyang Zhou⁷  Yan Huang⁸  Fangqian Li⁷  Jianwei Zhang¹  Yue Cai¹  Kun Wang⁶  Tenghui Ma³  Jiaming Zhou³  Huaiming Wang³  Jiayu Ling¹  Yonghua Cai³  Zehua Wu¹  Shuangling Luo³  Li Ling⁹  Yanhong Deng¹  Meijin Huang³  Liang Kang³  Wei Wang^1,11  Hui Wang³  Meng Qiu^1,12  Rongbo Lin^1,13  Haibo Zhang^1,15 

[1] Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University;Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases;Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University;Department of Medical Ultrasonics, The Sixth Affiliated Hospital of Sun Yat-sen University;Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University;Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute;Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University;Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University;Sun Yat-sen Center for Migrant Health Policy, School of Public Health, Sun Yat-sen University;Faculty of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University;Department of Gastrointestinal Oncology, The First People's Hospital of Foshan;Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University;Department of Gastrointestinal Oncology, Fujian Cancer Hospital;Fujian Medical University Cancer Hospital;Department of Oncology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine;The Second Clinical College, Guangzhou University of Chinese Medicine

关键词: Modified FOLFOXIRI;    Cetuximab;    Conversion therapy;    Colorectal cancer;    Liver metastasis;   

DOI  :  10.1634/theoncologist.2020-0563

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

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/m 2 ) plus mFOLFOXIRI (oxaliplatin 85 mg/m 2 , irinotecan 165 mg/m 2 , folinic acid 400 mg/m 2 , 5-fluorouracil 2,800 mg/m 2 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.

【 授权许可】

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