501OCALGB/SWOG 80405: PHASE III TRIAL OF IRINOTECAN/5-FU/LEUCOVORIN (FOLFIRI) OR OXALIPLATIN/5-FU/LEUCOVORIN (MFOLFOX6) WITH BEVACIZUMAB (BV) OR CETUXIMAB (CET) FOR PATIENTS (PTS) WITH EXPANDED RAS ANALYSES UNTREATED METASTATIC ADENOCARCINOMA OF THE COLON OR RECTUM (MCRC)
501OCALGB/SWOG 80405: PHASE III TRIAL OF IRINOTECAN/5-FU/LEUCOVORIN (FOLFIRI) OR OXALIPLATIN/5-FU/LEUCOVORIN (MFOLFOX6) WITH BEVACIZUMAB (BV) OR CETUXIMAB (CET) FOR PATIENTS (PTS) WITH EXPANDED RAS ANALYSES UNTREATED METASTATIC ADENOCARCINOMA OF THE COLON OR RECTUM (MCRC)
复制标题
501OCALGB/SWOG 80405：伊立替康/5-FU/亚叶酸 (FOLFIRI) 或奥沙利铂/5-FU/亚叶酸 (MFOLFOX6) 与贝伐珠单抗 (BV) 或西妥昔单抗 (CET) 联合治疗 RAS 扩大的患者 (PTS) 未经治疗的 III 期试验分析
DOI：
10.1093/annonc/mdu438.13
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发表时间：
2014
影响因子：
50.5
通讯作者：
A. Venook
中科院分区：
文献类型：
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作者：
H. Lenz;D. Niedzwiecki;F. Innocenti;C. Blanke;M. Mahony;B. O'Neil;J. Shaw;B. Polite;H. Hochster;J. Atkins;R. Goldberg;R. Mayer;R. Schilsky;M. Bertagnolli;A. Venook
目的：FOLFIRI或mFOLFOX6联合BV或CET是治疗MCRC的一线药物。最佳抗体组合是未知的。方法：RAS wt（密码子12和13）MCRC和性能状态0-1的患者接受FOLFIRI或mFOLFOX6（入组时MD/pt选择），随机分为CET 400 mg/m2 X 1，然后250 mg/m2 q2w或BV 5 mg/kg q2w。最初的研究包括未选择的MCRC患者接受FOLFIRI或mFOLFOX6，并随机分为CET、BV或两者。1420名患者累积后，研究修改如下：仅纳入w/ KRAS wt肿瘤患者（密码子12和13）。利用光束技术对所有wt - RAS外显子2进行扩展RAS检测，包括KRAS外显子3、4和NRAS外显子2、3和4，检测灵敏度为0.01%。后续Rx不强制执行。1°终点为总生存期（OS）。结果：在2005年11月至2012年3月期间，3058名未选择的患者入组，2334名KRAS wt患者随机化；最终N =1137（修订前符合回顾性KRAS测试333例，修订后804例），中位数f/u = xx mos；中位年龄59岁；61%的男性。化疗/ bv - 559;化疗/ cet - 578。FOLFIRI = 26.6%, mFOLFOX6 = 73.4%。来自xx例患者的肿瘤样本可用于扩展ras分析。我们在患有kras外显子2的患者中发现了xx%的kras外显子3和4突变以及NRAS外显子2、3和4突变。化疗/BV vs .化疗/CET治疗的wt RAS患者OS = xx (xx - xx) vs . xx (xx - x) mos；HR = xx (xx, xx) （p值= xxx）。PFS（研究者）：chemo/BV vs . chemo/CET: xxx (xx - xx) vs . xxx (xx - xx) mos。研究中的毒性和死亡与预期一致结论：更新的分析将在会议上展示。披露：H. Lenz：广告委员会Genentech/Roche， MerckKG， EMD， BMS。所有其他作者都声明没有利益冲突。
ABSTRACT Aim: FOLFIRI or mFOLFOX6, combined with BV or CET, are 1st-line treatments for MCRC. The optimal antibody combination is unknown. Methods: Pts with RAS wt (codons 12 and 13) MCRC and performance status 0-1 received FOLFIRI or mFOLFOX6 (MD/pt choice at enrollment) and randomized to either CET 400 mg/m2 X 1, then 250 mg/m2 qw or BV 5 mg/kg q2w. The original study included unselected MCRC pts receiving FOLFIRI or mFOLFOX6 and randomized to CET, BV or both. After 1420 pts accrued the study amended as follows: only pts w/ KRAS wt tumors (codon 12 and 13) were included. Accrual goal was 1142 pts Expanded RAS was tested in all wt ras exon 2 using beaming technology including KRAS exon 3,4 and NRAS exon 2, 3 and 4 with a detection sensitivity of 0.01%. Subsequent Rx not mandated. 1° endpoint was overall survival (OS). Results: Between 11/2005 and 3/2012, 3058 unselected pts enrolled, 2334 KRAS wt pts randomized; final N =1137 (333 pre-amend eligible retrospective KRAS test, 804 post-amend), median f/u = xx mos; Median age–59 y; 61% male. Chemo/BV–559; chemo/CET–578. FOLFIRI = 26.6%, mFOLFOX6 = 73.4%. From xx patients tumor samples were available for expanded ras analyses. We identified xx% mutations in kras exon 3 and 4 and NRAS in exon 2,3 and 4 in patients with wt KRAS exon2. The OS in patients with wt RAS treated with chemo/BV v. chemo/CET = xx (xx - xx) v. xx (xx - x) mos; HR = xx (xx, xx) (p value = xxx). PFS (by investigator): chemo/BV v. chemo/CET: xxx (xx - xx) v. xxx (xx - xx) mos. On-study toxicity and deaths as expected. Conclusions: Updated analysis will be shown at meeting. Disclosure: H. Lenz: Ad Board Genentech/Roche, MerckKG, EMD, BMS. All other authors have declared no conflicts of interest.