Venook Alan P, Niedzwiecki Donna, Lenz Heinz-Josef, Innocenti Federico, Fruth Briant, Meyerhardt Jeffrey A, Schrag Deborah, Greene Claire, O'Neil Bert H, Atkins James Norman, Berry Scott, Polite Blase N, O'Reilly Eileen M, Goldberg Richard M, Hochster Howard S, Schilsky Richard L, Bertagnolli Monica M, El-Khoueiry Anthony B, Watson Peter, Benson Al B, Mulkerin Daniel L, Mayer Robert J, Blanke Charles
University of California, San Francisco.
Department of Biostatistics and Bioinformatics and Alliance Statistics and Data Center, Duke University Medical Center, Durham, North Carolina.
JAMA. 2017 Jun 20;317(23):2392-2401. doi: 10.1001/jama.2017.7105.
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 vs bevacizumab 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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
将生物单克隆抗体与化疗细胞毒性药物联合使用可为晚期或转移性结直肠癌患者带来临床益处，但对于既往未接受治疗的患者，初始生物治疗的最佳选择尚不清楚。
确定在亚叶酸钙、氟尿嘧啶和奥沙利铂（mFOLFOX6）方案或亚叶酸钙、氟尿嘧啶和伊立替康（FOLFIRI）方案中添加西妥昔单抗与贝伐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时，哪种方案更具优势。
设计、设置和参与者：2005年11月至2012年3月期间，在美国和加拿大的国家临床试验网络中的社区和学术中心招募的患者（≥18岁），患有既往未接受治疗的晚期或转移性结直肠癌，其肿瘤为KRAS wt，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）治疗。最后一次随访日期为2015年12月15日。
西妥昔单抗与贝伐单抗分别与治疗医生和患者选择的mFOLFOX6或FOLFIRI化疗方案联合使用。
主要终点为总生存期。次要目标包括无进展生存期和总缓解率，由各研究点报告的经确认或未经确认的完全或部分缓解情况。
在1137例患者（中位年龄59岁；440例[39%]为女性）中，1074例（94%）符合入选标准。截至2015年12月15日，对263例存活患者的中位随访时间为47.4个月（范围0 - 110.7个月），82%的患者（1137例中的938例）出现疾病进展。西妥昔单抗化疗组的中位总生存期为30.0个月，贝伐单抗化疗组为29.0个月，分层风险比（HR）为0.88（95%CI，0.77 - 1.01；P = 0.08）。西妥昔单抗化疗组的中位无进展生存期为10.5个月，贝伐单抗化疗组为10.6个月，分层HR为0.95（95%CI，0.84 - 1.08；P = 0.45）。缓解率无显著差异，西妥昔单抗组和贝伐单抗组分别为59.6%和55.2%（差异4.4%，95%CI，1.0% - 9.0%，P = 0.13）。
在KRAS wt的未治疗晚期或转移性结直肠癌患者中，作为初始生物治疗，在化疗中添加西妥昔单抗与贝伐单抗的总生存期无显著差异。
clinicaltrials.gov标识符：NCT00265850。
