Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E1508).
Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E1508).
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DOI：
10.1002/cncr.30062
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发表时间：
2016-08-01
期刊：
影响因子：
6.2
通讯作者：
Schiller JH
中科院分区：
文献类型：
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作者：
Belani CP;Dahlberg SE;Rudin CM;Fleisher M;Chen HX;Takebe N;Velasco MR Jr;Tester WJ;Sturtz K;Hann CL;Shanks JC;Monga M;Ramalingam SS;Schiller JH
vismodegib对hedgehog通路的临床前靶向作用和cixutumumab对胰岛素样生长因子1受体的临床前靶向作用增强了化疗的疗效，并且还显示了对小细胞肺癌中导致疾病复发的肿瘤细胞部分的活性。新诊断的广泛期小细胞肺癌（SCLC-ED）患者随机接受4个21天周期的顺铂和依托泊苷单药治疗（第1天顺铂75 mg/m2，第1-3天依托泊苷100 mg/m2; A组）或与vismodegi B（口服150 mg/d; B组）或西妥昔单抗（第1天静脉内6 mg/kg/wk; C组）联合治疗。主要终点是无进展生存期（PFS）。在基线时使用Veridex CellSearch平台分离/计数循环肿瘤细胞（CTC）。152例合格患者接受了治疗。除了B组体力状态为0的比率较高（P = .03）外，3组之间的患者人口统计学和疾病特征平衡良好。A、B和C组的中位PFS时间分别为4.4、4.4和4.6个月;中位总生存期（OS）时间分别为8.8、9.8和10.1个月;缓解率分别为48%、56%和50%。这些结果的比较均无统计学显著性。基线时CTC计数低（≤100/7.5 mL）的患者的中位OS为10.5个月，CTC计数高的患者为7.2个月（风险比，1.74; P = .006）。在SCLC-ED患者的化疗中添加vismodegib或cixutumumab，PFS或OS没有显著改善。基线CTC计数低与良好的预后相关。
Preclinical targeting of the hedgehog pathway by vismodegib and of insulin-like growth factor 1 receptor by cixutumumab enhances the efficacy of chemotherapy and also demonstrates activity against the tumor cell fraction responsible for disease recurrence in small cell lung cancer. Patients with newly diagnosed extensive-stage small cell lung cancer (SCLC-ED) were randomized to receive four 21-day cycles of cisplatin and etoposide alone (cisplatin at 75 mg/m2 on day 1 and etoposide at 100 mg/m2 on days 1-3; arm A) or in combination with either vismodegib (150 mg/d by mouth; arm B) or cixutumumab (6 mg/kg/wk intravenously on day 1; arm C). The primary endpoint was progression-free survival (PFS). Circulating tumor cells (CTCs) were isolated/enumerated with the Veridex CellSearch platform at the baseline. One hundred fifty-two eligible patients were treated. Patient demographics and disease characteristics were well balanced between the 3 arms except for the higher rate with a performance status of 0 in arm B (P = .03). The median PFS times in arms A, B, and C were 4.4, 4.4, and 4.6 months, respectively; the median overall survival (OS) times were 8.8, 9.8, and 10.1 months, respectively; and the response rates were 48%, 56%, and 50%, respectively. None of the comparisons of these outcomes were statistically significant. The median OS was 10.5 months for those with low CTC counts (≤100/7.5 mL) at baseline and 7.2 months for those with high CTC counts (hazard ratio, 1.74; P = .006). There was no significant improvement in PFS or OS with the addition of either vismodegib or cixutumumab to chemotherapy in patients with SCLC-ED. A low baseline CTC count was associated with a favorable prognosis.