Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial.
Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial.
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DOI：
10.1001/jama.2017.7105
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发表时间：
2017-06-20
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影响因子：
--
通讯作者：
Blanke C
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作者：
Venook AP;Niedzwiecki D;Lenz HJ;Innocenti F;Fruth B;Meyerhardt JA;Schrag D;Greene C;O'Neil BH;Atkins JN;Berry S;Polite BN;O'Reilly EM;Goldberg RM;Hochster HS;Schilsky RL;Bertagnolli MM;El-Khoueiry AB;Watson P;Benson AB 3rd;Mulkerin DL;Mayer RJ;Blanke C
生物单抗联合化疗细胞毒药物为晚期或转移性结直肠癌患者提供了临床上的益处，但对于以前未接受治疗的患者，最初的生物治疗方案的最佳选择尚不清楚。目的：确定在亚叶酸钙、氟尿嘧啶和奥沙利铂联合方案(MFOLFOX6)或亚叶酸钙、氟尿嘧啶和伊立替康联合方案(FOLFIRI)中加入西妥昔单抗和贝伐珠单抗作为晚期或转移性KRAS野生型(Wt)结直肠癌一线治疗方案的优势。在美国和加拿大全国临床试验网络的社区和学术中心登记的患者(≥18岁)(2005年11月至2012年3月)，肿瘤为KRAS的未经治疗的晚期或转移性结直肠癌患者选择接受mFOLFOX6方案或FOLFIRI方案作为化疗，并随机接受西妥昔单抗(n=578)或贝伐单抗(n=559)。最后一次跟进日期是2015年12月15日。西妥昔单抗与贝伐单抗联合mFOLFOX6或FOLFIRI化疗方案由治疗医生和患者选择。主要终点是总体存活率。次要目标包括无进展存活率和总缓解率、现场报告的确认或未确认的完全或部分反应。在1137名患者(中位年龄59岁；440名女性[39%])中，1074名患者(94%)符合资格标准。截至2015年12月15日，263名存活患者的中位随访期为47.4月(范围0-110.7个月)，82%的患者(938/1137)经历了疾病进展。西妥昔单抗-化疗组和贝伐单抗-化疗组的中位总生存期分别为30.0个月和29.0个月，分层危险比(HR)为0.88(95%CI，0.77~1.01；P=0.08)。西妥昔单抗-化疗组和贝伐单抗-化疗组的中位无进展生存期分别为10.5个月和10.6个月，分层比为0.95(95%CI，0.84-1.08；P=.45)。西妥昔单抗和贝伐单抗的有效率分别为59.6%和55.2%，差异无统计学意义(分别为4.4%，95%CI，1.0%~9.0%，P=0.13)。在未经治疗的晚期或转移性结直肠癌患者中，西妥昔单抗与贝伐单抗加用作为初始生物治疗的化疗在总存活率上没有显著差异。ClinicalTrials.gov标识：NCT00265850
Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. To determine if the addition of cetuximab vsbevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer. Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015. Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient. The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response. Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0–110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77–1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84–1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13). Among patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment. clinicaltrials.gov identifier: NCT00265850
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