一项比较帕尼单抗联合氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）与单独 FOLFIRI 二线治疗转移性结直肠癌患者的随机 III 期研究。
Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer.
机构信息
University Hospital Ghent, Ghent, Belgium.
出版信息
J Clin Oncol. 2010 Nov 1;28(31):4706-13. doi: 10.1200/JCO.2009.27.6055. Epub 2010 Oct 4.
PURPOSE
Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status.
PATIENTS AND METHODS
Patients with mCRC, one prior chemotherapy regimen for mCRC, Eastern Cooperative Oncology Group performance status 0 to 2, and available tumor tissue for biomarker testing were randomly assigned 1:1 to panitumumab 6.0 mg/kg plus FOLFIRI versus FOLFIRI every 2 weeks. The coprimary end points of PFS and overall survival (OS) were independently tested and prospectively analyzed by KRAS status.
RESULTS
From June 2006 to March 2008, 1,186 patients were randomly assigned 1:1 and received treatment. KRAS status was available for 91% of patients: 597 (55%) with wild-type (WT) KRAS tumors, and 486 (45%) with mutant (MT) KRAS tumors. In the WT KRAS subpopulation, when panitumumab was added to chemotherapy, a significant improvement in PFS was observed (hazard ratio [HR] = 0.73; 95% CI, 0.59 to 0.90; P = .004); median PFS was 5.9 months for panitumumab-FOLFIRI versus 3.9 months for FOLFIRI. A nonsignificant trend toward increased OS was observed; median OS was 14.5 months versus 12.5 months, respectively (HR = 0.85, 95% CI, 0.70 to 1.04; P = .12); response rate was improved to 35% versus 10% with the addition of panitumumab. In patients with MT KRAS, there was no difference in efficacy. Adverse event rates were generally comparable across arms with the exception of known toxicities associated with anti-EGFR therapy.
CONCLUSION
Panitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS 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，可改善化疗耐药的转移性结直肠癌（mCRC）的无进展生存期（PFS）。本试验根据肿瘤 KRAS 状态评估了帕尼单抗联合氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）与单独使用 FOLFIRI 治疗 mCRC 初始治疗失败后的疗效和安全性。
患者和方法
mCRC 患者，先前接受过一种 mCRC 化疗方案，东部肿瘤协作组体能状态 0-2 分，且有可供生物标志物检测的肿瘤组织，被随机 1:1 分配接受帕尼单抗 6.0mg/kg 联合 FOLFIRI 或 FOLFIRI 每 2 周治疗。PFS 和总生存期（OS）是本试验的主要终点，且按 KRAS 状态进行了独立检测和前瞻性分析。
结果
从 2006 年 6 月至 2008 年 3 月，共 1186 例患者被随机 1:1 分配并接受治疗。91%的患者 KRAS 状态可评估：597 例（55%）为 KRAS 野生型（WT）肿瘤，486 例（45%）为 KRAS 突变型（MT）肿瘤。在 WT KRAS 亚组中，当帕尼单抗联合化疗时，PFS 显著改善（风险比[HR] = 0.73；95%CI，0.59 至 0.90；P =.004）；帕尼单抗-FOLFIRI 组中位 PFS 为 5.9 个月，而 FOLFIRI 组为 3.9 个月。OS 也有改善趋势，但无统计学意义；中位 OS 分别为 14.5 个月和 12.5 个月（HR = 0.85，95%CI，0.70 至 1.04；P =.12）；加入帕尼单抗后，缓解率提高至 35%，而单独使用 FOLFIRI 组为 10%。在 MT KRAS 患者中，疗效无差异。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一般相似。
结论
帕尼单抗联合 FOLFIRI 可显著改善 PFS，作为 KRAS WT mCRC 二线治疗的耐受性良好。
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