Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First-Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With KRAS Wild-Type Tumors in Metastatic Colorectal Cancer
Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First-Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With KRAS Wild-Type Tumors in Metastatic Colorectal Cancer
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DOI：
10.1200/jco.2015.61.2887
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发表时间：
2015-11-10
影响因子：
45.3
通讯作者：
Heinemann, Volker
中科院分区：
文献类型：
--
作者：
Modest, Dominik P.;Stintzing, Sebastian;Heinemann, Volker
目的：在FIRE-3试验（FOLFIRI联合西妥昔单抗[A组]或贝伐单抗[B组]）中，我们研究了KRAS野生型转移性结直肠癌患者的后续治疗选择和疗效，特别关注二线治疗。患者和方法后续治疗（第二或第三次）的开始定义为使用一种不属于先前治疗方案的抗肿瘤药物。我们评估了后续治疗的选择、持续时间和疗效，并确定了后续治疗对FIRE-3患者结局的影响。结果592例意向治疗人群中，414例（69.9%）接受了二线治疗，256例（43.2%）接受了三线治疗。在随后的治疗线中，47.1%最初分配到A组的患者接受了贝伐单抗，52.2%最初分配到B组的患者接受了西妥昔单抗或帕尼单抗。随后，55.9% （A组）和53.2% （B组）的患者使用奥沙利铂。研究组a和b的中位持续时间分别为5.0和3.2个月（P < 0.001）。无进展（6.5 v 4.7个月，风险比0.68,95% CI 0.54至0.85,P < 0.001）和总生存期(16.3 v 13.2个月，风险比0.70,95% CI 0.55至0.88；P < 0.0021)，与b组相比，A组患者从二线治疗开始的时间更长。结论我们的数据表明，药物应用顺序可能比单一药物暴露更重要。在RAS野生型肿瘤患者中，一线应用抗表皮生长因子受体定向治疗可能为促进包括抗血管生成药物在内的有效后续治疗提供有利条件。(C) 2015年由美国临床肿瘤学会出版
PurposeWe investigated choice and efficacy of subsequent treatment, with special focus on second-line therapy, in the FIRE-3 trial (FOLFIRI plus cetuximab [arm A] or bevacizumab [arm B]) for patients with KRAS wild-type metastatic colorectal cancer.Patients and MethodsStart of subsequent-line (second or third) therapy was defined as use of an antitumor drug that was not part of the previous regimen. We evaluated choice, duration, and efficacy of subsequent therapy and determined the impact of subsequent-line treatment on outcome of patients in FIRE-3.ResultsOf 592 patients in the intent-to-treat population, 414 (69.9%) received second-line and 256 (43.2%) received third-line therapy. In subsequent treatment lines, 47.1% of patients originally assigned to arm A received bevacizumab, and 52.2% originally assigned to arm B received either cetuximab or panitumumab. Oxaliplatin was subsequently used in 55.9% (arm A) and 53.2% (arm B) of patients. Second-line therapy was administered for a median duration of 5.0 versus 3.2 months (P < .001) in study arm A versus B. Progression-free (6.5 v 4.7 months; hazard ratio, 0.68; 95% CI, 0.54 to 0.85; P < .001) and overall survival (16.3 v 13.2 months; hazard ratio, 0.70; 95% CI, 0.55 to 0.88; P < .0021) from start of second-line therapy were longer in patients in arm A compared with arm B.ConclusionOur data suggest that the sequence of drug application might be more important than exposure to single agents. In patients with RAS wild-type tumors, first-line application of anti-epidermal growth factor receptor-directed therapy may represent a favorable condition for promoting effective subsequent therapy including antiangiogenic agents. (C) 2015 by American Society of Clinical Oncology