Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study
Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study
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DOI：
10.1200/jco.2009.27.4860
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发表时间：
2010-11-01
影响因子：
45.3
通讯作者：
Gansert, Jennifer
中科院分区：
文献类型：
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作者：
Douillard, Jean-Yves;Siena, Salvatore;Gansert, Jennifer
目的帕尼单抗是一种全人源抗表皮生长因子受体 (EGFR) 单克隆抗体，可改善无进展生存期 (PFS)，被批准作为化疗难治性转移性结直肠癌 (mCRC) 患者的单一疗法。帕尼单抗联合化疗治疗转移性结直肠癌以确定疗效 (PRIME) 的随机试验旨在评估帕尼单抗联合输注氟尿嘧啶、亚叶酸和奥沙利铂 (FOLFOX4) 与单独使用 FOLFOX4 作为 mCRC 初始治疗的疗效和安全性。 患者和方法在这项多中心、III 期试验中，患者既往未接受过 mCRC 化疗，东部合作肿瘤学 (Eastern Cooperative Oncology)组表现状态为 0 至 2，并且可用于生物标志物测试的组织被随机分配为 1:1 接受帕尼单抗-FOLFOX4 与 FOLFOX4。主要终点是 PFS；总生存期（OS）是次要终点。根据肿瘤 KRAS 状态，在意向治疗的基础上对结果进行前瞻性分析。结果 随机分配的 1,183 名患者中，93% 的患者可获得 KRAS 结果。在野生型 (WT) KRAS 层中，与 FOLFOX4 相比，帕尼单抗-FOLFOX4 显着改善了 PFS（中位 PFS 分别为 9.6 个月和 8.0 个月；风险比 [HR]，0.80；95% CI，0.66 至 0.97；P = .02）。与 FOLFOX4 相比，帕尼单抗-FOLFOX4 的 OS 也没有显着增加（中位 OS 分别为 23.9 个月和 19.7 个月；HR，0.83；95% CI，0.67 至 1.02；P = 0.072）。在突变 KRAS 层中，帕尼单抗-FOLFOX4 组与 FOLFOX4 组相比，PFS 显着降低（HR，1.29；95% CI，1.04 至 1.62；P = 0.02），中位 OS 分别为 15.5 个月与 19.3 个月（HR，1.24；95% CI，0.98 至 1.57；P = 0.02）。 .068）。除已知与抗 EGFR 治疗相关的毒性外，各组的不良事件发生率通常相当。 结论 这项研究表明，帕尼单抗-FOLFOX4 具有良好的耐受性，并且显着改善 WT KRAS 肿瘤患者的 PFS，并强调了 KRAS 检测对于 mCRC 患者的重要性。
PurposePanitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC.Patients and MethodsIn this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1: 1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status.ResultsKRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy.ConclusionThis study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.