Karin Potthoff, Norbert Marschner, Lothar Müller, Stephan Sahm, Christian Lerchenmüller, Reinhard Depenbusch, Emil Boller, Beate Niemeier, Ute Zirrgiebel, Hans Tesch
{"title":"ERBIMOX的最终结果：一项随机II期研究，修饰FOLFOX7联合或不联合西妥昔单抗作为KRAS野生型转移性结直肠癌的一线治疗。","authors":"Karin Potthoff, Norbert Marschner, Lothar Müller, Stephan Sahm, Christian Lerchenmüller, Reinhard Depenbusch, Emil Boller, Beate Niemeier, Ute Zirrgiebel, Hans Tesch","doi":"10.1007/s12029-025-01260-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The combination of FOLFOX/FOLFIRI with an EGFR-antibody (cetuximab/panitumumab) is a first-line standard for RAS wild-type metastatic colorectal cancer (mCRC). The OPTIMOX stop-and-go regimen, which reduces oxaliplatin-induced neuropathy, and fluorouracil/folinic acid (FU/FA) were standard maintenance-therapies in the pre-antibody era. Whether an EGFR-antibody adds value to the OPTIMOX strategy in the RAS wild-type setting remains unknown.</p><p><strong>Methods: </strong>In the open-label, randomized, multicenter phase II ERBIMOX trial, patients with KRAS wild-type mCRC received either first-line induction-therapy with 8 cycles of mFOLFOX7 followed by maintenance-therapy with FU/FA (OPTIMOX arm) or mFOLFOX7 + cetuximab followed by FU/FA + cetuximab (ERBIMOX arm). Primary objective was to demonstrate superiority of additional cetuximab to mFOLFOX7 during induction/maintenance-therapy. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The trial is registered at EudraCT (No.2006-002744-28).</p><p><strong>Results: </strong>From 2006-2011, 138 patients with KRAS wild-type mCRC from 23 German sites were randomly assigned to either OPTIMOX (N = 63) or ERBIMOX (N = 75). ORR numerically favored the ERBIMOX arm (64.0% vs. 54.0%, P = 0.3071). Median PFS (ERBIMOX vs. OPTIMOX) was 9.6 vs. 8.8 months (P = 0.7612), median OS 25.6 vs. 30.9 months (P = 0.5821). Most common grade 3/4 adverse events (AEs) were skin reactions (21.9% vs. 2.1%) and gastrointestinal disorders (13.5% vs. 9.5%). No cetuximab-related deaths occurred.</p><p><strong>Conclusion: </strong>In treatment-naïve KRAS wild-type mCRC, adding cetuximab to mFOLFOX7 resulted in numerically higher ORR than mFOLFOX alone, but no statistically significant differences in ORR, PFS or OS; probably because of the premature stop due to poor recruitment. The safety profile was as expected, with few discontinuations.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"141"},"PeriodicalIF":1.6000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Final Results of ERBIMOX: A Randomized Phase II Study of Modified FOLFOX7 With or Without Cetuximab as First-Line Treatment for KRAS Wild-type Metastatic Colorectal Cancer.\",\"authors\":\"Karin Potthoff, Norbert Marschner, Lothar Müller, Stephan Sahm, Christian Lerchenmüller, Reinhard Depenbusch, Emil Boller, Beate Niemeier, Ute Zirrgiebel, Hans Tesch\",\"doi\":\"10.1007/s12029-025-01260-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The combination of FOLFOX/FOLFIRI with an EGFR-antibody (cetuximab/panitumumab) is a first-line standard for RAS wild-type metastatic colorectal cancer (mCRC). The OPTIMOX stop-and-go regimen, which reduces oxaliplatin-induced neuropathy, and fluorouracil/folinic acid (FU/FA) were standard maintenance-therapies in the pre-antibody era. Whether an EGFR-antibody adds value to the OPTIMOX strategy in the RAS wild-type setting remains unknown.</p><p><strong>Methods: </strong>In the open-label, randomized, multicenter phase II ERBIMOX trial, patients with KRAS wild-type mCRC received either first-line induction-therapy with 8 cycles of mFOLFOX7 followed by maintenance-therapy with FU/FA (OPTIMOX arm) or mFOLFOX7 + cetuximab followed by FU/FA + cetuximab (ERBIMOX arm). Primary objective was to demonstrate superiority of additional cetuximab to mFOLFOX7 during induction/maintenance-therapy. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The trial is registered at EudraCT (No.2006-002744-28).</p><p><strong>Results: </strong>From 2006-2011, 138 patients with KRAS wild-type mCRC from 23 German sites were randomly assigned to either OPTIMOX (N = 63) or ERBIMOX (N = 75). ORR numerically favored the ERBIMOX arm (64.0% vs. 54.0%, P = 0.3071). Median PFS (ERBIMOX vs. OPTIMOX) was 9.6 vs. 8.8 months (P = 0.7612), median OS 25.6 vs. 30.9 months (P = 0.5821). Most common grade 3/4 adverse events (AEs) were skin reactions (21.9% vs. 2.1%) and gastrointestinal disorders (13.5% vs. 9.5%). No cetuximab-related deaths occurred.</p><p><strong>Conclusion: </strong>In treatment-naïve KRAS wild-type mCRC, adding cetuximab to mFOLFOX7 resulted in numerically higher ORR than mFOLFOX alone, but no statistically significant differences in ORR, PFS or OS; probably because of the premature stop due to poor recruitment. The safety profile was as expected, with few discontinuations.</p>\",\"PeriodicalId\":15895,\"journal\":{\"name\":\"Journal of Gastrointestinal Cancer\",\"volume\":\"56 1\",\"pages\":\"141\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Gastrointestinal Cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/s12029-025-01260-6\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Gastrointestinal Cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s12029-025-01260-6","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：FOLFOX/FOLFIRI联合egfr抗体（西妥昔单抗/帕尼单抗）是治疗RAS野生型转移性结直肠癌（mCRC）的一线标准。OPTIMOX停走方案，减少奥沙利铂诱导的神经病变，和氟尿嘧啶/亚叶酸（FU/FA）是抗体前时代的标准维持疗法。在RAS野生型环境下，egfr抗体是否会增加OPTIMOX策略的价值尚不清楚。方法：在开放标签，随机，多中心II期ERBIMOX试验中，KRAS野生型mCRC患者接受一线诱导治疗8周期mFOLFOX7，然后使用FU/FA （OPTIMOX组）维持治疗，或mFOLFOX7 +西妥昔单抗，然后使用FU/FA +西妥昔单抗（ERBIMOX组）。主要目的是证明在诱导/维持治疗期间额外使用西妥昔单抗优于mFOLFOX7。主要终点为客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）和安全性。该试验已在edract注册（No.2006-002744-28）。结果：从2006年到2011年，来自德国23个地点的138例KRAS野生型mCRC患者被随机分配到OPTIMOX （N = 63）或ERBIMOX （N = 75）。ORR数值上有利于艾比莫司组（64.0% vs. 54.0%, P = 0.3071）。中位PFS （ERBIMOX vs. OPTIMOX）为9.6 vs. 8.8个月（P = 0.7612），中位OS为25.6 vs. 30.9个月（P = 0.5821）。最常见的3/4级不良事件（ae）是皮肤反应（21.9%对2.1%）和胃肠道疾病（13.5%对9.5%）。未发生西妥昔单抗相关死亡。结论：在treatment-naïve KRAS野生型mCRC中，西妥昔单抗与mFOLFOX7联合治疗的ORR数值高于单用mFOLFOX7，但ORR、PFS和OS无统计学差异；可能是因为招募不到位导致的过早停止。安全性与预期一致，几乎没有中断。
Final Results of ERBIMOX: A Randomized Phase II Study of Modified FOLFOX7 With or Without Cetuximab as First-Line Treatment for KRAS Wild-type Metastatic Colorectal Cancer.
Background: The combination of FOLFOX/FOLFIRI with an EGFR-antibody (cetuximab/panitumumab) is a first-line standard for RAS wild-type metastatic colorectal cancer (mCRC). The OPTIMOX stop-and-go regimen, which reduces oxaliplatin-induced neuropathy, and fluorouracil/folinic acid (FU/FA) were standard maintenance-therapies in the pre-antibody era. Whether an EGFR-antibody adds value to the OPTIMOX strategy in the RAS wild-type setting remains unknown.
Methods: In the open-label, randomized, multicenter phase II ERBIMOX trial, patients with KRAS wild-type mCRC received either first-line induction-therapy with 8 cycles of mFOLFOX7 followed by maintenance-therapy with FU/FA (OPTIMOX arm) or mFOLFOX7 + cetuximab followed by FU/FA + cetuximab (ERBIMOX arm). Primary objective was to demonstrate superiority of additional cetuximab to mFOLFOX7 during induction/maintenance-therapy. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The trial is registered at EudraCT (No.2006-002744-28).
Results: From 2006-2011, 138 patients with KRAS wild-type mCRC from 23 German sites were randomly assigned to either OPTIMOX (N = 63) or ERBIMOX (N = 75). ORR numerically favored the ERBIMOX arm (64.0% vs. 54.0%, P = 0.3071). Median PFS (ERBIMOX vs. OPTIMOX) was 9.6 vs. 8.8 months (P = 0.7612), median OS 25.6 vs. 30.9 months (P = 0.5821). Most common grade 3/4 adverse events (AEs) were skin reactions (21.9% vs. 2.1%) and gastrointestinal disorders (13.5% vs. 9.5%). No cetuximab-related deaths occurred.
Conclusion: In treatment-naïve KRAS wild-type mCRC, adding cetuximab to mFOLFOX7 resulted in numerically higher ORR than mFOLFOX alone, but no statistically significant differences in ORR, PFS or OS; probably because of the premature stop due to poor recruitment. The safety profile was as expected, with few discontinuations.
期刊介绍：
The Journal of Gastrointestinal Cancer is a multidisciplinary medium for the publication of novel research pertaining to cancers arising from the gastrointestinal tract.The journal is dedicated to the most rapid publication possible.The journal publishes papers in all relevant fields, emphasizing those studies that are helpful in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus. In addition, the Journal of Gastrointestinal Cancer publishes basic and translational scientific information from studies providing insight into the etiology and progression of cancers affecting these organs. New insights are provided from diverse areas of research such as studies exploring pre-neoplastic states, risk factors, epidemiology, genetics, preclinical therapeutics, surgery, radiation therapy, novel medical therapeutics, clinical trials, and outcome studies.In addition to reports of original clinical and experimental studies, the journal also publishes: case reports, state-of-the-art reviews on topics of immediate interest or importance; invited articles analyzing particular areas of pancreatic research and knowledge; perspectives in which critical evaluation and conflicting opinions about current topics may be expressed; meeting highlights that summarize important points presented at recent meetings; abstracts of symposia and conferences; book reviews; hypotheses; Letters to the Editors; and other items of special interest, including:Complex Cases in GI Oncology: This is a new initiative to provide a forum to review and discuss the history and management of complex and involved gastrointestinal oncology cases. The format will be similar to a teaching case conference where a case vignette is presented and is followed by a series of questions and discussion points. A brief reference list supporting the points made in discussion would be expected.
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