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Abstract：
BACKGROUND: Crizotinib is a tyrosine kinase inhibitor (TKI) effective in ALK/ROS-1/c-MET positive non-small cell lung cancer (NSCLC) patients. Bevacizumab is an antiangiogenic monoclonal antibody, and improves clinical benefit of NSCLC in combination with EGFR-TKIs or chemotherapy. However, the efficacy and safety of crizotinib plus bevacizumab in treating naive ALK/ROS-1/c-MET positive NSCLC patients have not been studied.
METHODS: In this open-label, single-arm, prospective observational study, locally advanced or metastatic ALK rearrangement/ROS-1 fusion/c-MET amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death. Primary end point was progressive free survival (PFS), secondary end points were duration of response (DOR), overall response rate (ORR), disease control rate (DCR) and safety. Patients receiving ≥1 cycle of treatment were evaluated.
RESULTS: Fourteen patients were eligible for analyzing between June 2016 and October 2017. There were 12 patients with ALK rearrangement, 1 patient with ROS-1 fusion, and 1 patient with c-MET amplification. The median follow-up time was 42.8 months. The median PFS and DOR of the patients with ALK rearrangement were 13.9 and 14.8 months respectively. Of the 12 patients, 7 gained partial response, 5 gained stable disease. The ORR and DCR were 58.3% and 100%. The PFS were 12.9 months and 1.9 months for patient with ROS-1 fusion or c-MET amplification. The most two common treatment-related adverse events were fatigue (28.6%) and rash (21.4%). 3 patients discontinued therapy because of liver damage or hemoptysis.
CONCLUSIONS: This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive ALK rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ROS-1/c-MET positive NSCLC patients.
METHODS: In this open-label, single-arm, prospective observational study, locally advanced or metastatic ALK rearrangement/ROS-1 fusion/c-MET amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death. Primary end point was progressive free survival (PFS), secondary end points were duration of response (DOR), overall response rate (ORR), disease control rate (DCR) and safety. Patients receiving ≥1 cycle of treatment were evaluated.
RESULTS: Fourteen patients were eligible for analyzing between June 2016 and October 2017. There were 12 patients with ALK rearrangement, 1 patient with ROS-1 fusion, and 1 patient with c-MET amplification. The median follow-up time was 42.8 months. The median PFS and DOR of the patients with ALK rearrangement were 13.9 and 14.8 months respectively. Of the 12 patients, 7 gained partial response, 5 gained stable disease. The ORR and DCR were 58.3% and 100%. The PFS were 12.9 months and 1.9 months for patient with ROS-1 fusion or c-MET amplification. The most two common treatment-related adverse events were fatigue (28.6%) and rash (21.4%). 3 patients discontinued therapy because of liver damage or hemoptysis.
CONCLUSIONS: This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive ALK rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ROS-1/c-MET positive NSCLC patients.
摘要：
背景：克唑替尼是一种酪氨酸激酶抑制剂（TKI），对ALK/ROS-1/c-MET阳性非小细胞肺癌（NSCLC）患者有效。贝伐单抗是一种抗血管生成的单克隆抗体，联合EGFR-TKIs或化疗可提高NSCLC的临床获益。然而,克唑替尼联合贝伐单抗治疗初治ALK/ROS-1/c-MET阳性NSCLC患者的疗效和安全性尚未得到研究.
方法：在此开放标签中，单臂,前瞻性观察研究，局部晚期或转移性ALK重排/ROS-1融合/c-MET扩增NSCLC患者接受克唑替尼(250mg,每日2次口服)和贝伐单抗(7.5mg/kg,每3周静脉注射)治疗,直至疾病进展或不耐受毒性或死亡.主要终点是无进展生存期（PFS），次要终点为缓解持续时间(DOR),总反应率（ORR），疾病控制率(DCR)和安全性。对接受≥1个治疗周期的患者进行评估。
结果：2016年6月至2017年10月期间，有14例患者符合分析条件。有12例ALK重排患者，1例ROS-1融合患者，1例c-MET扩增患者。中位随访时间为42.8个月。ALK重排患者的中位PFS和DOR分别为13.9个月和14.8个月。在12名患者中，7获得部分响应，5获得了稳固的病情。ORR和DCR分别为58.3%和100%。ROS-1融合或c-MET扩增患者的PFS分别为12.9个月和1.9个月。最常见的两种治疗相关不良事件是疲劳（28.6%）和皮疹（21.4%）。3例患者因肝损伤或咯血停止治疗。
结论：本研究表明，克唑替尼联合贝伐单抗治疗初治ALK重排非小细胞肺癌患者，毒性相对耐受。我们的结果表明，克唑替尼联合贝伐单抗可能是ALK/ROS-1/c-MET阳性NSCLC患者的一种有希望的治疗策略。
方法：在此开放标签中，单臂,前瞻性观察研究，局部晚期或转移性ALK重排/ROS-1融合/c-MET扩增NSCLC患者接受克唑替尼(250mg,每日2次口服)和贝伐单抗(7.5mg/kg,每3周静脉注射)治疗,直至疾病进展或不耐受毒性或死亡.主要终点是无进展生存期（PFS），次要终点为缓解持续时间(DOR),总反应率（ORR），疾病控制率(DCR)和安全性。对接受≥1个治疗周期的患者进行评估。
结果：2016年6月至2017年10月期间，有14例患者符合分析条件。有12例ALK重排患者，1例ROS-1融合患者，1例c-MET扩增患者。中位随访时间为42.8个月。ALK重排患者的中位PFS和DOR分别为13.9个月和14.8个月。在12名患者中，7获得部分响应，5获得了稳固的病情。ORR和DCR分别为58.3%和100%。ROS-1融合或c-MET扩增患者的PFS分别为12.9个月和1.9个月。最常见的两种治疗相关不良事件是疲劳（28.6%）和皮疹（21.4%）。3例患者因肝损伤或咯血停止治疗。
结论：本研究表明，克唑替尼联合贝伐单抗治疗初治ALK重排非小细胞肺癌患者，毒性相对耐受。我们的结果表明，克唑替尼联合贝伐单抗可能是ALK/ROS-1/c-MET阳性NSCLC患者的一种有希望的治疗策略。
