Gadgeel Shirish, Goss Glenwood, Soria Jean-Charles, Felip Enriqueta, Georgoulias Vassilis, Lu Shun, Cobo Manuel, Syrigos Konstantinos, Lee Ki Hyeong, Göker Erdem, Guclu Salih Z, Isla Dolores, Morabito Alessandro, Dupuis Nicholas, Bühnemann Claudia, Krämer Nicole, Solca Flavio, Ehrnrooth Eva, Ardizzoni Andrea
Karmanos Cancer Institute/Wayne State University, 4100 John R, Detroit, MI 48201, USA.
The Ottawa Hospital Research Institute and University of Ottawa, 501 Smyth Rd, Ottawa, Ontario K1H 8L6, Canada.
Lung Cancer. 2017 Jul;109:101-108. doi: 10.1016/j.lungcan.2017.05.010. Epub 2017 May 11.
Identification of biomarkers associated with clinical benefit may be crucial in establishing optimal treatment choice for patients with squamous cell carcinoma (SCC) of the lung after first-line chemotherapy. In this study, the ability of the VeriStrat serum protein test to predict differential clinical benefit with afatinib versus erlotinib, and the association of VeriStrat status with clinical outcomes irrespective of EGFR-TKI used, was assessed in a retrospective analysis of the phase III LUX-Lung 8 trial.
Pretreatment plasma samples were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Spectra were evaluated to assign a VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) classification. Overall survival (OS), progression-free survival, and other endpoints were assessed with respect to pretreatment VeriStrat status; OS was the primary efficacy variable. Outcomes with other efficacy endpoints were similar.
Of 795 patients randomized in LUX-Lung 8, 675 were classified (VS-G: 412; VS-P: 263). In the VS-G group, OS was significantly longer with afatinib versus erlotinib (HR 0.79 [95% CI: 0.63-0.98]). In the VS-P group, there was no significant difference in OS between afatinib and erlotinib (HR 0.90 [0.70-1.16]). However, there was no interaction between VeriStrat classification and treatment group for OS (p=0.5303). OS was significantly longer in VS-G versus VS-P patients, both in the overall VeriStrat-classified population (HR 0.41 [0.35-0.49]) and afatinib-treated patients (HR 0.40 [0.31-0.51]). Multivariate analysis showed that VeriStrat was an independent predictor of OS in afatinib-treated patients, regardless of ECOG PS or best response to first-line chemotherapy.
VS-G classification is strongly associated with favorable survival outcomes with either afatinib or erlotinib compared with VS-P classification. In VS-G patients, survival outcomes with afatinib are superior to those with erlotinib. VeriStrat classification may guide treatment decisions in patients with SCC of the lung. ClinicalTrials.gov registration number: NCT01523587.
识别与临床获益相关的生物标志物对于为一线化疗后的肺鳞状细胞癌（SCC）患者确定最佳治疗方案可能至关重要。在本研究中，通过对III期LUX-Lung 8试验的回顾性分析，评估了VeriStrat血清蛋白检测预测阿法替尼与厄洛替尼不同临床获益的能力，以及VeriStrat状态与临床结局的关联（无论使用何种EGFR-TKI）。
使用基质辅助激光解吸电离飞行时间质谱对预处理血浆样本进行分析。评估光谱以确定VeriStrat“良好”（VS-G）或VeriStrat“不良”（VS-P）分类。根据预处理VeriStrat状态评估总生存期（OS）、无进展生存期和其他终点；OS是主要疗效变量。其他疗效终点的结果相似。
在LUX-Lung 8试验中随机分组的795例患者中，675例被分类（VS-G：412例；VS-P：263例）。在VS-G组中，阿法替尼治疗的OS显著长于厄洛替尼（HR 0.79 [95% CI：0.63 - 0.98]）。在VS-P组中，阿法替尼和厄洛替尼的OS无显著差异（HR 0.90 [0.70 - 1.16]）。然而，VeriStrat分类与治疗组之间在OS方面无相互作用（p = 0.5303）。在整个VeriStrat分类人群（HR 0.41 [0.35 - 0.49]）和阿法替尼治疗的患者（HR 0.40 [0.31 - 0.51]）中，VS-G患者的OS均显著长于VS-P患者。多变量分析表明，在阿法替尼治疗的患者中，VeriStrat是OS的独立预测因素，无论ECOG PS或对一线化疗的最佳反应如何。
与VS-P分类相比，VS-G分类与阿法替尼或厄洛替尼的良好生存结局密切相关。在VS-G患者中，阿法替尼的生存结局优于厄洛替尼。VeriStrat分类可能指导肺SCC患者的治疗决策。ClinicalTrials.gov注册号：NCT01523587。
