可切除非小的新辅助治疗?不止一种选择?

免疫组化抗体神器

好评必备! 免费下载

  A Phase I/II Study of NeoadjuvantCisplatin, Docetaxel and Nintedanib for Resectable Non-Small Cell Lung Cancer
  Clinical Cancer Research 2020 March 19
  PURPOSE: Nintedanib enhances the activityof chemotherapy in metastatic NSCLC. In this phase I/II study, we assessedsafety and efficacy of nintedanib plus neoadjuvant chemotherapy, using majorpathologic response (MPR) as primary endpoint.
  目的:Nintedanib在转移性非小细胞肺癌中提高了化疗的疗效。在这项I/II期临床试验中,拟探索其在与化疗联合的新辅助治疗NSCLC中的安全性和有效性,本研究使用主要病理学缓解MPR作为研究终点。
  EXPERIMENTAL DESIGN: Eligible patients hadstage IB (≥4 cm)-IIIA resectable NSCLC. A safety run-in phase was followed byan expansion phase with nintedanib 200 mg PO bid (28 days), followed by 3cycles of cisplatin (75 mg/m2), docetaxel (75 mg/m2) q21 days plus nintedanib,followed by surgery. With 33 planned patients, the study had 90% power todetect an MPR increase from 15% to 35%.
  试验设计:纳入IB-IIIA期可切除非小细胞肺癌的患者。患者术前先接受nintedanib并从常规安全剂量逐步扩增至200mg 口服bid(28天),然后接受三个周期的顺铂及多西他赛治疗。在入组的33名患者中,本研究拟获取MPR从15%到35%的疗效基于90%的把握度。
  RESULTS: 21 patients (stages I/II/III,N=1/8/12) were treated. One of 15 patients treated with nintedanib 200 mgachieved MPR (7%, 95% CI 0.2%-32%). Best ORR in 20 evaluable patients was 30%(6/20, 95% CI 12%-54%). 12-month RFS and OS were 66% (95% CI 47%-93%) and 91%(95% CI, 79%-100%), respectively. Most frequent treatment-related G3-4toxicities were transaminitis and electrolyte abnormalities. Based on aninterim analysis the study was discontinued for futility. Higher levels of CD3+and cytotoxic CD3+CD8+ T cells were found in treated tumors of patients whowere alive than in those who died (652.8 vs. 213.4 cells/mm2, P=0.048; 142.3vs. 35.6 cells/mm2, P=0.018).
  结果:21名患者接受了治疗(I期1名,II期8名,III期12名)。在15名接受了全剂量的nintedanib患者中1名(7%,95CI 0.2-32%)患者达到了MPR。20名可评估的患者中客观缓解率最高为30%(6/20,95% CI 12-54%),12个月的无复发生存期为66%(95% CI:47-93%),12个月的总生存期为91%(95 CI:79-100%)。治疗相关的3-4级副反应主要为转氨酶和电解质异常。基于中期分析,该研究因未达预期而中止。存活患者的肿瘤中CD3 +和细胞毒性CD3+、CD8+ T细胞的水平高于死亡患者(652.8 vs. 213.4 /mm2,P=0.048;142.3 vs. 35.6 /mm2,P=0.018 )。
  CONCLUSIONS: Although tolerated,neoadjuvant nintedanib plus chemotherapy did not increase MPR rate compared tochemotherapy historical controls. Additional studies of the combination in thissetting are not recommended. Post-treatment levels of tumor infiltrating Tcells were associated with patient survival. Use of MPR facilitates the rapidevaluation of neoadjuvant therapies.
  结论:尽管nintedanib的耐受性较好,但其联合化疗与经典化疗的对比并未增加MPR率。基于此背景不建议在这种情况下对该组合进行其他研究。治疗后肿瘤浸润性T细胞水平与患者生存率相关。新辅助治疗中MPR有助于疗效的快速评估。
  这项研究来自MD Anderson团队,其中负责手术部分的是胸心血管外科的Boris Sepesi教授。近几年MD Anderson也开展了新辅助免疫治疗的临床试验。
  简单查了一下Nintedanib这个药3月初刚被FDA通过用于间质性肺疾病。但这项研究的MPR实在是差强人意,相比于免疫治疗15-40%的MPR率。并不是哪个药都能够从晚期成功应用于早期新辅助的。配一张药物的通路图吧。Nintedanib 竞争性抑制 nonreceptortyrosine kinases (nRTKs) 和 receptor tyrosinekinases (RTKs),其靶标包括PDGFR、FGFR、VEGFR等。
可切除非小的新辅助治疗?不止一种选择?
可切除非小的新辅助治疗?不止一种选择?
责任编辑: 夢奕新
0 0 0

扫一扫下载91360客户端