Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)
Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)
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DOI：
10.1200/jco.2011.39.6036
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发表时间：
2012-05-10
影响因子：
45.3
通讯作者：
Chau, Ian
中科院分区：
文献类型：
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作者：
Dewdney, Alice;Cunningham, David;Chau, Ian
目的评估高危直肠癌放化疗前新辅助化疗中添加西妥昔单抗。患者和方法可手术磁共振成像定义的高危直肠癌患者接受四个周期的卡培他滨/奥沙利铂 (CAPOX)，然后接受卡培他滨放化疗、手术和辅助 CAPOX（四个周期）或 相同的方案加上每周西妥昔单抗 (CAPOX + C)。主要终点是 KRAS/BRAF 野生型肿瘤患者的完全缓解（CR；病理学 CR，或者在未接受手术的患者中，放射学 CR）。次要终点是放射学反应 (RR)、无进展生存期 (PFS)、总生存期 (OS)、野生型和总体群体的安全性以及分子生物标志物分析。 结果 165 名符合条件的患者被随机分配。 149 个可评估肿瘤中的 90 个 (60%) 为 KRAS 或 BRAF 野生型（CAPOX，n = 44；CAPOX + C，n = 46），在这些患者中，添加西妥昔单抗并未改善主要终点 CR（分别为 9% vs 11%；P = 1.0；比值比，1.22）或 PFS（风险比 [HR]，0.65；P = .363）。西妥昔单抗显着改善 RR（CAPOX vs CAPOX + C：化疗后，分别为 51% vs 71%；P = .038；放化疗后，分别为 75% vs 93%；P = .028）和 OS（HR，0.27；P = .034）。 CAPOX + C 组中皮肤毒性和腹泻更常见。 结论 西妥昔单抗导致 KRAS/BRAF 野生型直肠癌患者的 RR 和 OS 显着增加，但未达到改善 CR 的主要终点。
PurposeTo evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer.Patients and MethodsPatients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX + C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis.ResultsOne hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX + C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [ HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX + C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX + C arm.ConclusionCetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.