Randomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
Randomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.22.02543
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发表时间：
2023-05
影响因子：
45.3
通讯作者：
David H. Johnson;L. Fehrenbacher;W. Novotny;R. Herbst;J. Nemunaitis;D. Jablons;C. Langer;R. Devore-R.-D
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文献类型：
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作者：
David H. Johnson;L. Fehrenbacher;W. Novotny;R. Herbst;J. Nemunaitis;D. Jablons;C. Langer;R. Devore-R.-D
目的观察贝伐单抗联合卡铂和紫杉醇治疗晚期或复发性非小细胞肺癌的疗效和安全性。患者和方法在一项II期试验中，99名患者被随机分配到贝伐单抗7.5（n = 32）或15 mg/kg（n = 35）加卡铂（曲线下面积= 6）和紫杉醇（200 mg/m2）每3周或卡铂和紫杉醇单独（n = 32）。主要疗效终点为疾病进展时间和最佳确认缓解率。在疾病进展时，对照组的患者可以选择接受单药贝伐珠单抗15 mg/kg，每3周一次。结果与对照组相比，卡铂和紫杉醇联合贝伐单抗（15 mg/kg）治疗导致更高的缓解率（31.5% v18.8%），更长的中位进展时间（7.4 v4.2个月）和生存期适度增加（17.7 v14.9个月）。在19名交叉使用单药贝伐单抗的对照患者中，5名患者病情稳定，1年生存率为47%。出血是最突出的不良事件，表现为两种不同的临床模式：轻微粘膜皮肤出血和大咯血。大咯血与鳞状细胞组织学、肿瘤坏死和空洞以及疾病位置靠近主要血管有关。结论贝伐单抗联合卡铂和紫杉醇可改善晚期或复发性非小细胞肺癌患者的总体疗效和至进展时间。非鳞状细胞组织学患者似乎是结局改善且安全性风险可接受的亚群。
PURPOSE To investigate the efficacy and safety of bevacizumab plus carboplatin and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer. PATIENTS AND METHODS In a phase II trial, 99 patients were randomly assigned to bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). Primary efficacy end points were time to disease progression and best confirmed response rate. On disease progression, patients in the control arm had the option to receive single-agent bevacizumab 15 mg/kg every 3 weeks. RESULTS Compared with the control arm, treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5% v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest increase in survival (17.7 v 14.9 months). Of the 19 control patients that crossed over to single-agent bevacizumab, five experienced stable disease, and 1-year survival was 47%. Bleeding was the most prominent adverse event and was manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and major hemoptysis. Major hemoptysis was associated with squamous cell histology, tumor necrosis and cavitation, and disease location close to major blood vessels. CONCLUSION Bevacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.