Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers.
Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers.
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DOI：
10.1097/jto.0b013e31829923ec
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Rizvi NA
中科院分区：
文献类型：
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作者：
Chaft JE;Rusch V;Ginsberg MS;Paik PK;Finley DJ;Kris MG;Price KA;Azzoli CG;Fury MG;Riely GJ;Krug LM;Downey RJ;Bains MS;Sima CS;Rizk N;Travis WD;Rizvi NA
贝伐单抗提高晚期非小细胞肺癌（NSCLC）患者的生存率。这项II期临床试验评估了贝伐单抗加入新辅助化疗对可切除的非鳞状NSCLC的影响。可切除的IB-IIIA期非鳞状NSCLC患者接受贝伐单抗治疗，2周后进行影像学检查以评估单药效果。然后他们接受了2个周期的贝伐单抗和4个周期的顺铂和多西他赛，然后手术切除。切除的患者符合贝伐单抗辅助治疗的条件。主要终点是病理降分期率（从治疗前临床阶段减少到治疗后病理阶段）。次要终点包括总生存期、安全性和放射反应。50名患者入组。34例（68%）为临床IIIA期。所有3剂新辅助贝伐单抗均用于40/50例患者。6例（12%）患者因贝伐单抗相关不良事件而停药。降期率（38%）、化疗反应率（45%）和围手术期并发症率（12%）与历史数据相当。单药贝伐单抗未观察到部分反应，但18%的患者出现新的瘤内空化，病理反应有改善的趋势（57%对21%，p=0.07）。主要病理反应（≥90%的治疗效果）与3年生存率相关（100% vs 49%, p=0.01）。KRAS突变型NSCLC患者（0/10）没有病理反应，而野生型KRAS患者（11/31）有病理反应。虽然术前贝伐单抗加化疗是可行的，但它并没有改善未选择的患者的降期。单药贝伐单抗后新的空化是潜在的生物标志物。对于kras突变肿瘤，需要其他的治疗策略。
Bevacizumab improves survival in patients with advanced non-small cell lung cancer (NSCLC). This phase II clinical trial assessed the effects of the addition of bevacizumab to neoadjuvant chemotherapy in resectable non-squamous NSCLC. Patients with resectable stage IB-IIIA non-squamous NSCLC were treated with bevacizumab followed by imaging 2 weeks later to assess single agent effect. They then received 2 cycles of bevacizumab with 4 cycles of cisplatin and docetaxel followed by surgical resection. Resected patients were eligible for adjuvant bevacizumab. The primary endpoint was the rate of pathological downstaging (decrease from pretreatment clinical stage to post-treatment pathological stage). Secondary endpoints included overall survival, safety and radiologic response. Fifty patients were enrolled. Thirty-four (68%) were clinical stage IIIA. All 3 doses of neoadjuvant bevacizumab were delivered to 40/50 patients. Six (12%) patients discontinued due to bevacizumab-related adverse events. The rate of downstaging (38%), response to chemotherapy (45%), and perioperative complications (12%) were comparable to historical data. No partial responses were observed to single-agent bevacizumab but 18% developed new intratumoral cavitation with a trend toward improved pathologic response (57% vs. 21%, p=0.07). A major pathologic response (≥90% treatment effect) was associated with survival at 3 years (100% vs. 49%, p=0.01). No patients with KRAS-mutant NSCLC (0/10) had a pathologic response as compared with 11/31 with wild-type KRAS. While preoperative bevacizumab plus chemotherapy was feasible, it did not improve downstaging in unselected patients. New cavitation after single-agent bevacizumab is a potential biomarker. Alternative strategies are needed for KRAS-mutant tumors.