Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer
Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer
复制标题
DOI：
10.1080/0284186x.2016.1253866
复制
发表时间：
2017-01-01
期刊：
影响因子：
3.1
通讯作者：
Harmenberg, Johan
中科院分区：
文献类型：
--
作者：
Bergqvist, Michael;Holgersson, Georg;Harmenberg, Johan
背景资料：本研究的主要目的是比较接受IGF-1 R通路调节剂AXL 1717（AXL）治疗的患者和接受多西他赛（DCT）治疗的患者在12周时的无进展生存期（PFS）。共有99例既往接受过治疗的患者，需要额外治疗的鳞状细胞癌（SCC）或腺癌（AC）亚型的局部晚期或转移性非小细胞肺癌（NSCLC）患者随机接受300或400 mg AXL每日BID治疗（58例患者）或DCT 75 mg/m2（41例患者）作为单药治疗，每种NSCLC亚型的比例为3：2，3周为1周期。患者在主要研究治疗期接受最多4个治疗cycles.Results：12周PFS率，中位PFS和总生存期（OS），以及PFS和OS的Kaplan-Meier风险比，治疗组间未显示任何统计学显著差异。对于主要终点，与DCT组（39. 0%）相比，AXL组第12周无进展的患者百分比（25. 9%）较低，但差异无统计学显著性。治疗后出现的不良反应（TEAE）的发生率最显着的差异是治疗相关的3/4级中性粒细胞减少症的发生率较低的AXL.Conclusion：这些结果表明，无论是治疗局部晚期或转移性NSCLC时，是上级的其他治疗。考虑到AXL组3/4级中性粒细胞减少症的发生率较低，这种治疗值得进一步研究。
Background: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).Material and methods: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400mg of AXL as daily BID treatment (58 patients) or DCT given as 75mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3: 2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.Results: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression- free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.Conclusion: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.