A randomized, placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer
A randomized, placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer
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DOI：
10.1093/annonc/mdt057
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发表时间：
2013-07-01
影响因子：
50.5
通讯作者：
Choo, S-P
中科院分区：
文献类型：
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作者：
Cohn, A. L.;Tabernero, J.;Choo, S-P
背景：目前可用于突变型KRAS转移性结直肠癌（mCRC）的靶向药物是贝伐单抗和阿柏西普。我们评估了conatumumab的有效性和安全性，（一种针对人类死亡受体5的激动性单克隆抗体）和ganitumab（一种针对1型胰岛素样生长因子受体的单克隆抗体）联合标准FOLFIRI化疗作为突变型KRAS mCRC患者的二线治疗。对基于氟尿嘧啶和奥沙利铂的化疗难治的突变型KRAS转移性结肠或直肠腺癌患者以1：1的比例随机分组：1例接受静脉FOLFIRI + conatumumab 10 mg/kg（A组）、ganitumab 12 mg/kg（B组）或安慰剂（C组）Q2 W。主要终点是无进展生存期（PFS）。结果：共有155例患者随机分组。A、B和C组的中位PFS为6.5个月（HR，0.69; P = 0.147），4.5个月（HR，1.01; P = 0.998）和4.6个月;中位总生存期为12.3个月（HR，0.89; P = 0.650）、12.4个月（HR，1.27; P = 0.357）和12.0个月;客观缓解率分别为14%、8%和2%。A/B/C组中最常见的≥ 3级不良事件包括中性粒细胞减少（30%/25%/18%）和腹泻（18%/2%/10%）。结论：Conatumumab，而不是ganitumab，联合FOLFIRI与PFS改善的趋势相关。两种组合均具有可接受的毒性。
Background: Targeted agents presently available for mutant KRAS metastatic colorectal cancer (mCRC) are bevacizumab and aflibercept. We evaluated the efficacy and safety of conatumumab (an agonistic monoclonal antibody against human death receptor 5) and ganitumab (a monoclonal antibody against the type 1 insulin-like growth factor receptor) combined with standard FOLFIRI chemotherapy as a second-line treatment in patients with mutant KRAS mCRC.Patients and methods: Patients with mutant KRAS metastatic adenocarcinoma of the colon or rectum refractory to fluoropyrimidine- and oxaliplatin-based chemotherapy were randomized 1: 1: 1 to receive intravenous FOLFIRI plus conatumumab 10 mg/kg (Arm A), ganitumab 12 mg/kg (Arm B), or placebo (Arm C) Q2W. The primary end point was progression-free survival (PFS).Results: In total, 155 patients were randomized. Median PFS in Arms A, B, and C was 6.5 months (HR, 0.69; P = 0.147), 4.5 months (HR, 1.01; P = 0.998), and 4.6 months, respectively; median overall survival was 12.3 months (HR, 0.89; P = 0.650), 12.4 months (HR, 1.27; P = 0.357), and 12.0 months; and objective response rate was 14%, 8%, and 2%. The most common grade >= 3 adverse events in Arms A/B/C included neutropenia (30%/25%/18%) and diarrhea (18%/2%/10%).Conclusions: Conatumumab, but not ganitumab, plus FOLFIRI was associated with a trend toward improved PFS. Both combinations had acceptable toxicity.