PMID- 32687588 OWN - NLM STAT- MEDLINE DCOM- 20201221 LR - 20201221 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 3 IP - 7 DP - 2020 Jul 1 TI - Effect of Reduced-Dose Capecitabine Plus Cetuximab as Maintenance Therapy for RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Clinical Trial. PG - e2011036 LID - 10.1001/jamanetworkopen.2020.11036 [doi] LID - e2011036 AB - IMPORTANCE: Fluorouracil-based chemotherapy combined with anti-epidermal growth factor receptor/vascular endothelial growth factor therapy is the standard first-line treatment for metastatic colorectal cancer followed by low-intensity maintenance therapy to balance the clinical efficacy and adverse effects (AEs). However, there have been concerns about the AEs of capecitabine plus cetuximab as a maintenance therapy in patients with RAS wild-type metastatic colorectal cancer. OBJECTIVE: To evaluate the biological activity and safety of capecitabine plus cetuximab as a novel maintenance therapy for RAS wild-type metastatic colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: This phase 2 prospective clinical trial was conducted from April 29, 2016, to April 29, 2019, at 5 centers in China. Patients diagnosed as having RAS wild-type metastatic colorectal cancer were recruited to receive fluorouracil-based cytotoxic agents combined with cetuximab followed by capecitabine plus cetuximab for maintenance therapy. Forty-seven patients with histologically confirmed metastatic colorectal cancer and genetic test results showing a wild-type RAS were enrolled in maintenance therapy. INTERVENTIONS: Induction therapy for patients with RAS wild-type metastatic colorectal cancer was 8 to 12 cycles of fluorouracil-based chemotherapy combined with cetuximab. After stable disease status or better was achieved, reduced-dose capecitabine plus cetuximab was administered for maintenance therapy. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival during maintenance therapy. The secondary end points were total progression-free survival, overall survival, quality of life, safety, and toxic effects of treatment. RESULTS: Forty-seven patients were enrolled in maintenance therapy, with a median age of 52 years (range, 25-81 years) and 32 (68%) of them being men. The median maintenance progression-free survival was 7.2 (95% CI, 5.8-8.6) months. The median progression-free survival was 12.7 (95% CI, 11.8-15.4) months. The median overall survival was 27.4 (95% CI, 21.4-35.5) months. Grade 3 to 4 AEs during induction therapy included neutropenia (4 patients [9%]), diarrhea (4 patients [9%]), nausea or vomiting (3 patients [6%]), rash acneiform (10 patients [21%]), and hand-foot syndrome (8 patients [17%]). Grade 3 to 4 AEs during maintenance therapy included diarrhea (2 patients [4%]), rash acneiform (8 patients [17%]), and hand-foot syndrome (5 patients [11%]). CONCLUSIONS AND RELEVANCE: Reduced-dose capecitabine plus cetuximab after initial chemotherapy is a novel maintenance therapy for patients with RAS wild-type metastatic colorectal cancer that achieved good outcomes and tolerable nonserious AEs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02717923. FAU - Wang, Lu AU - Wang L AD - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Liu, Ying AU - Liu Y AD - Department of Medical Oncology of Zhengzhou University Affiliated Cancer Hospital, Henan Cancer Hospital, Zhengzhou, Henan, China. FAU - Yin, Xianli AU - Yin X AD - Gastroenterology and Urology Department, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China. FAU - Fang, Weijia AU - Fang W AD - Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Xiong, Jianping AU - Xiong J AD - Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. FAU - Zhao, Ben AU - Zhao B AD - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Zhang, Mingsheng AU - Zhang M AD - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Zou, Yanmei AU - Zou Y AD - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Qiu, Hong AU - Qiu H AD - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Yuan, Xianglin AU - Yuan X AD - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. LA - eng SI - ClinicalTrials.gov/NCT02717923 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200701 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 6804DJ8Z9U (Capecitabine) RN - PQX0D8J21J (Cetuximab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Capecitabine/*administration & dosage/therapeutic use MH - Cetuximab/*administration & dosage/therapeutic use MH - Colorectal Neoplasms/*drug therapy MH - *Dose-Response Relationship, Drug MH - Drug Therapy/methods/*standards/statistics & numerical data MH - Female MH - Humans MH - Male MH - Middle Aged MH - Prospective Studies PMC - PMC7372324 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2020/07/21 06:00 MHDA- 2020/12/22 06:00 PMCR- 2020/07/20 CRDT- 2020/07/21 06:00 PHST- 2020/07/21 06:00 [entrez] PHST- 2020/07/21 06:00 [pubmed] PHST- 2020/12/22 06:00 [medline] PHST- 2020/07/20 00:00 [pmc-release] AID - 2768375 [pii] AID - zoi200431 [pii] AID - 10.1001/jamanetworkopen.2020.11036 [doi] PST - epublish SO - JAMA Netw Open. 2020 Jul 1;3(7):e2011036. doi: 10.1001/jamanetworkopen.2020.11036.