Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147.
Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147.
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DOI：
10.1016/j.clcc.2013.12.002
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发表时间：
2014-06
影响因子：
3.4
通讯作者：
Alliance for Clinical Trials in Oncology
中科院分区：
文献类型：
--
作者：
Huang J;Nair SG;Mahoney MR;Nelson GD;Shields AF;Chan E;Goldberg RM;Gill S;Kahlenberg MS;Quesenberry JT;Thibodeau SN;Smyrk TC;Grothey A;Sinicrope FA;Webb TA;Farr GH Jr;Pockaj BA;Berenberg JL;Mooney M;Sargent DJ;Alberts SR;Alliance for Clinical Trials in Oncology
在切除结肠癌的第三阶段随机试验N0147中，早期试验包括使用和不使用西妥昔单抗的FOLFIRI(伊立替康、5-氟尿嘧啶和亚叶酸钙)的治疗臂，以及使用和不使用西妥昔单抗的FOLFOX(奥沙利铂、5-氟尿嘧啶和亚叶酸钙)。在接受FOLFIRI加西妥昔单抗的小组中，注意到可能受益的证据。然而，在等待随机试验的结果之前，FOLFIRI加西妥昔单抗不应被视为辅助治疗的选择。使用或不使用西妥昔单抗的两组FOLFIRI患者最初被纳入NCCTG(北方中心癌症治疗组)N0147的随机III期组间临床试验。当其他当代试验显示使用伊立替康作为辅助治疗没有好处时，含有FOLFIRI的手臂被停止使用。我们报告了随机使用或不使用西妥昔单抗的FOLFIRI患者的临床结果。切除后，患者被随机分成12个双周周期的FOLFIRI，使用或不使用西妥昔单抗。KRAS(柯尔斯滕大鼠肉瘤病毒癌基因同源)突变状态在中心实验室进行了回顾性检测。主要终点是无病生存(DFS)。次要终点包括总生存期(OS)和毒性。106名患者接受FOLFIRI治疗，40名患者接受FOLFIRI加西妥昔单抗治疗。中位随访期为5.95年(0.1~7.0年)。在整个组和野生型KRAS患者中，加入西妥昔单抗显示出改善DFS(危险比[HR]，0.53；95%CI，0.26-1.1；P=.09)和OS(HR，0.45；95%CI，0.17-1.16；P=.10)的趋势。西妥昔单抗组与单用FOLFIRI组相比，≥3级非血液学不良反应显著增加(68%比46%；P=0.02)。佐剂FOLFIRI导致的3年DFS比FOLFOX预期的要短。在这一小部分切除的III期结肠癌患者中，在FOLFIRI中加入西妥昔单抗与改善DFS和OS的无显著趋势相关。然而，考虑到这项分析的局限性，没有添加生物制剂的FOLFOX仍然是切除的III期结肠癌辅助治疗的标准。
In the randomized phase III trial N0147 for resected colon cancer, the early trial versions included treatment arms of FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) with and without cetuximab, in addition to FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) with and without cetuximab. In the small group receiving FOLFIRI plus cetuximab evidence of possible benefit was noted. However, pending results of a randomized trial, FOLFIRI plus cetuximab should not be considered as an option for adjuvant therapy. Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab. After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity. One hundred and six patients received FOLFIRI and 40 received FOLFIRI plus cetuximab. Median follow-up was 5.95 years (range, 0.1–7.0 years). The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95% CI, 0.26–1.1; P = .09) and OS (HR, 0.45; 95% CI, 0.17–1.16; P = .10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. Grade ≥ 3 nonhematologic adverse effects were significantly increased in the cetuximab versus FOLFIRI-alone arm (68% vs. 46%; P = .02). Adjuvant FOLFIRI resulted in a 3-year DFS less than that expected for FOLFOX. In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage III colon cancer.
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