Rocky Mountain Cancer Center, Denver, CO, USA.
Clin Colorectal Cancer. 2011 Sep;10(3):171-7. doi: 10.1016/j.clcc.2011.03.022. Epub 2011 Apr 28.
This prospective analysis evaluated the effect of tumor KRAS status on efficacy of second-line panitumumab plus folinic acid/5-fluorouracil/irinotecan (FOLFIRI).
This phase 2, open-label, single-arm study enrolled patients with unresectable, measurable metastatic colorectal cancer (mCRC) after failure of first-line treatment with oxaliplatin-based chemotherapy plus bevacizumab. Patients received panitumumab 6 mg/kg plus FOLFIRI every 2 weeks until disease progression or intolerability. Tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) were performed by the investigators every 8 weeks from weeks 8-32 and every 12 weeks thereafter. KRAS status was determined by real-time polymerase chain reaction (PCR) on DNA extracted from fixed tumor sections. Efficacy endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS). Safety endpoints included incidence of adverse events (AEs). Endpoints were evaluated by tumor KRAS status.
Of 116 patients enrolled, 109 patients with known tumor KRAS status received treatment; 59% had wild-type KRAS, and 41% had mutant KRAS. Fifteen patients (23%) with wild-type KRAS and 7 patients (16%) with mutant KRAS had a complete or partial response to treatment. Median PFS was 26 weeks (95% CI, 19-33 weeks) and 19 weeks (95% CI, 12-25 weeks) in the wild-type KRAS and mutant KRAS strata, respectively. Median OS was 50 weeks (95% CI, 39-76 weeks) and 31 weeks (95% CI, 23-47 weeks) in wild-type KRAS and mutant KRAS strata, respectively. Skin-related toxicities (86% of all patients) and diarrhea (74%) were the most common AEs.
Panitumumab plus FOLFIRI numerically improved objective response rate, PFS, and OS in favor of patients with wild-type KRAS tumors. The safety profile was consistent with panitumumab plus FOLFIRI trials in similar patient populations.
本前瞻性分析评估了肿瘤 KRAS 状态对二线帕尼单抗联合亚叶酸、5-氟尿嘧啶、伊立替康（FOLFIRI）疗效的影响。
这是一项 2 期、开放标签、单臂研究，纳入了一线奥沙利铂联合化疗加贝伐单抗治疗失败后无法切除、可测量的转移性结直肠癌（mCRC）患者。患者接受帕尼单抗 6mg/kg 联合 FOLFIRI 治疗，每 2 周 1 次，直至疾病进展或不耐受。研究者每 8 周（第 8-32 周）和此后每 12 周根据实体瘤反应评价标准（RECIST）进行肿瘤评估。通过实时聚合酶链反应（PCR）测定固定肿瘤切片中提取的 DNA 的 KRAS 状态。疗效终点包括客观缓解率、无进展生存期（PFS）和总生存期（OS）。安全性终点包括不良事件（AE）发生率。根据肿瘤 KRAS 状态评估终点。
在 116 例入组患者中，109 例患者具有已知的肿瘤 KRAS 状态，接受了治疗；59%为 KRAS 野生型，41%为 KRAS 突变型。15 例（23%）KRAS 野生型患者和 7 例（16%）KRAS 突变型患者对治疗有完全或部分缓解。野生型 KRAS 亚组和突变型 KRAS 亚组的中位 PFS 分别为 26 周（95%CI，19-33 周）和 19 周（95%CI，12-25 周）。野生型 KRAS 亚组和突变型 KRAS 亚组的中位 OS 分别为 50 周（95%CI，39-76 周）和 31 周（95%CI，23-47 周）。皮肤相关毒性（所有患者的 86%）和腹泻（74%）是最常见的 AE。
帕尼单抗联合 FOLFIRI 在客观缓解率、PFS 和 OS 方面均有改善，有利于 KRAS 野生型肿瘤患者。安全性与类似患者人群中帕尼单抗联合 FOLFIRI 试验一致。
