Centre René Gauducheau, Nantes, France.
J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.
PURPOSE: Panitumumab, 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 METHODS: In 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. RESULTS: KRAS 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. CONCLUSION: This 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.
目的：帕尼单抗是一种完全人源化的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），已被批准作为化疗耐药转移性结直肠癌（mCRC）患者的单药治疗药物。帕尼单抗联合化疗治疗转移性结直肠癌以确定疗效的随机试验（PRIME）旨在评估帕尼单抗联合氟尿嘧啶、亚叶酸钙和奥沙利铂（FOLFOX4）与 FOLFOX4 单药治疗作为 mCRC 初始治疗的疗效和安全性。
方法：在这项多中心、III 期试验中，未接受过 mCRC 化疗、东部合作肿瘤学组（ECOG）体能状态为 0 至 2 分且有可用于生物标志物检测的组织的患者，以 1:1 的比例随机分配接受帕尼单抗-FOLFOX4 或 FOLFOX4 治疗。主要终点是无进展生存期（PFS）；总生存期（OS）是次要终点。根据肿瘤 KRAS 状态进行前瞻性意向治疗分析。
结果：93%的 1183 例随机分配患者可获得 KRAS 结果。在野生型（WT）KRAS 亚组中，与 FOLFOX4 相比，帕尼单抗-FOLFOX4 显著改善了 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=0.02）。也观察到帕尼单抗-FOLFOX4 与 FOLFOX4 相比 OS 有非显著增加（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）。在突变型 KRAS 亚组中，与 FOLFOX4 相比，帕尼单抗-FOLFOX4 组的 PFS 显著降低（HR，1.29；95%CI，1.04 至 1.62；P=0.02），中位 OS 分别为 15.5 个月和 19.3 个月（HR，1.24；95%CI，0.98 至 1.57；P=0.068）。除了与抗 EGFR 治疗相关的已知毒性外，各治疗组的不良反应发生率通常相当。
结论：这项研究表明，帕尼单抗-FOLFOX4 耐受性良好，可显著改善 WT KRAS 肿瘤患者的 PFS，并强调了 KRAS 检测对 mCRC 患者的重要性。
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