{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:52:49Z","timestamp":1783486369212,"version":"3.55.0"},"reference-count":36,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"1","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Zhangjiang Biotechnology Co., Ltd."},{"name":"Shanghai Zhangjiang Biotechnology Co., Ltd."},{"name":"Chinese National Major Project","award":["2012ZX09101103"],"award-info":[{"award-number":["2012ZX09101103"]}]},{"name":"Chinese National Major Project","award":["2013ZX09101002-001-001"],"award-info":[{"award-number":["2013ZX09101002-001-001"]}]},{"name":"Chinese National Major Project","award":["2008ZX09312"],"award-info":[{"award-number":["2008ZX09312"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Commun"],"published-print":{"date-parts":[[2019,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n The 5\n \u2010<\/jats:bold>\n fluorouracil\/leucovorin plus oxaliplatin (FOLFOX) regimen is the standard first\u2010line treatment for metastatic colorectal cancer (mCRC), however, the optimal second\u2010line regimen for\n KRAS<\/jats:italic>\n wild\u2010type mCRC patients is still investigational. In this study, we aimed to determine the clinical efficacy and safety of CMAB009 plus irinotecan compared to irinotecan\u2010only as a second\u2010line regimen for treating\n KRAS<\/jats:italic>\n wild\u2010type mCRC patients.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Patients with\n KRAS<\/jats:italic>\n wild\u2010type mCRC who had previously failed to respond to FOLFOX treatment were randomly assigned in a 2:1 ratio, to receive CMAB009 plus irinotecan or irinotecan\u2010only. Patients receiving irinotecan\u2010only were permitted to switch to CMAB009 therapy on disease progression and were grouped as the sequential\u2010CMAB009 arm. The primary endpoints were overall response rate (ORR) and median progression\u2010free survival (PFS). The secondary endpoints were median overall survival (OS), disease control rate (DCR), clinical benefit rate (CBR), and duration of response (DOR).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The CMAB009 plus irinotecan arm demonstrated significantly improved ORR (33.2% vs. 12.8%;\n P<\/jats:italic>\n < 0.001) and longer median PFS (169 days vs. 95 days;\n P<\/jats:italic>\n < 0.001) as compared to the irinotecan\u2010only arm. Patients receiving CMAB009 plus irinotecan also demonstrated improved DCR (80.1% vs. 65.2%,\n P<\/jats:italic>\n < 0.001), CBR (30.0% vs. 14.6%,\n P<\/jats:italic>\n < 0.001), and DOR (210 days vs. 109 days;\n P<\/jats:italic>\n < 0.001) as compared to irinotecan\u2010only. However, patients treated with CMAB009 had an increased risk of skin rash (66.9% vs. 5.5%,\n P<\/jats:italic>\n < 0.001) and paronychia (9.8% vs. 0.0%,\n P<\/jats:italic>\n < 0.001). Anti\u2010drug antibodies (ADA) were detected in 3.6% of patients, and only 0.9% of patients who received CMAB009 experienced hypersensitivity reactions. In patients receiving sequential\u2010CMAB009 therapy after failure with irinotecan, their median PFS was 84 days (95% CI 65 to 113 days). The median OS was 425 days for patients receiving CMAB009 plus irinotecan and 401 days for those with sequential\u2010CMAB009 (\n P<\/jats:italic>\n = 0.940).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Treatment with CMAB009 plus irinotecan was found to be a superior second\u2010line regimen in comparison to irinotecan\u2010only in\n KRAS<\/jats:italic>\n wild\u2010type mCRC patients. Further, switching to CMAB009 can be considered as an efficient third\u2010line of treatment after treatment failure with second\u2010line irinotecan\u2010only.\n <\/jats:p>\n \n Trial registration<\/jats:italic>\n ClinicalTrials.gov<\/jats:ext-link>\n : NCT01550055, retrospectively registered on March 9, 2012.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s40880-019-0374-8","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T09:06:19Z","timestamp":1558688779000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CMAB009 plus irinotecan versus irinotecan\u2010only as second\u2010line treatment after fluoropyrimidine and oxaliplatin failure in\n KRAS<\/i>\n wild\u2010type metastatic colorectal cancer patients: promising findings from a prospective, open\u2010label, randomized, phase III trial"],"prefix":"10.34133","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8450-7583","authenticated-orcid":false,"given":"Yuankai","family":"Shi","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"Fudan University Shanghai Cancer Center","place":["Shanghai, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Xu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Military Medical Sciences","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital","place":["Shanghai, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cheng","sequence":"additional","affiliation":[{"name":"Jilin Cancer Hospital","place":["Changchun, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Tumor Hospital of Hebei Province","place":["Shijiazhuang, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Sun","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Anhui Medical University","place":["Hefei, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigui","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Provincial Cancer Hospital","place":["Fuzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Bai","sequence":"additional","affiliation":[{"name":"Chinese People's Liberation Army General Hospital","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital","place":["Hangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"He","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Luo","sequence":"additional","affiliation":[{"name":"Hunan Cancer Hospital","place":["Changsha, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhehai","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Cancer Hospital","place":["Jinan, P. R. 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