Asklepios Fachkliniken GmbH, Gauting, Germany.
Tennessee Oncology, Nashville, Tennessee, USA.
Oncologist. 2018 Jun;23(6):654-e58. doi: 10.1634/theoncologist.2017-0690. Epub 2018 Feb 7.
The lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations.Future efforts with agents like anti-EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents.
Epidermal growth factor-like domain 7 (EGFL7) is an extracellular matrix-associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti-EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum-based therapy for advanced or recurrent nonsquamous non-small cell lung cancer (NS-NSCLC).
Patients ( = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21-day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months.
The progression-free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0-2.8; = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5-2.2; = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab.
There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first-line NS-NSCLC.
在这项非小细胞肺癌的 II 期试验中，抗 EGFL7 联合标准贝伐珠单抗和化疗的疗效不佳，与结直肠癌观察到的益处一致，这突出了在未选择人群中增强 VEGF 抑制疗效的挑战。未来应根据血管生成抑制剂的药效学和预测性生物标志物开发进展，指导使用抗 EGFL7 等药物。
表皮生长因子样结构域 7（EGFL7）是一种细胞外基质相关蛋白，在血管生成过程中上调，支持内皮细胞存活。这项 II 期试验评估了抗 EGFL7 抗体帕萨珠单抗与贝伐珠单抗联合铂类为基础的治疗方案用于晚期或复发性非鳞状非小细胞肺癌（NS-NSCLC）的疗效。
患者（ = 104）随机分为安慰剂或帕萨珠单抗（600mg）联合贝伐珠单抗（15mg/kg）和卡铂/紫杉醇，每 21 天周期的第 1 天给药。卡铂和紫杉醇最多给药 6 个周期。贝伐珠单抗和帕萨珠单抗/安慰剂最多给药 24 个月。
无进展生存期（PFS）的风险比（HR）为 1.7（95%置信区间[CI]，1.0-2.8； = .047）。帕萨珠单抗组的中位 PFS 为 6.7 个月，安慰剂组为 8.1 个月。总生存期（OS）的 HR 为 1.1（95%CI，0.5-2.2； = .847）。帕萨珠单抗组的客观缓解率（ORR）为 29%，安慰剂组为 56%。总体安全性和耐受性与贝伐珠单抗的既定毒性特征一致。
帕萨珠单抗联合贝伐珠单抗和化疗用于一线治疗非小细胞肺癌没有疗效证据。
