Background: The VeriStrat test provides accurate predictions of outcomes in all lines of therapy for patients with non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic role of VeriStrat in patients enrolled on the MARQUEE phase III trial of tivantinib plus erlotinib (T+E) versus placebo plus erlotinib (P+E) in previously treated patients with advanced NSCLC.
Methods: Pretreatment plasma samples were available for 996 patients and were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to generate VeriStrat labels (good, VS-G, or poor, VS-P).
Results: Overall, no significant benefit in overall survival (OS) and progression-free survival (PFS) were observed for the addition of tivantinib to erlotinib. Regardless of treatment arm, patients who were classified as VS-G had significantly longer PFS (3.8 mo for T+E arm, 2.0 mo for P+E arm) and OS (11.6 mo for T+E, 10.2 mo for P+E arm) than patients classified as VS-P (PFS: 1.9 mo for both arms, hazard ratio [HR], 0.584; 95% confidence interval [CI], 0.468-0.733; p < .0001 for T+E, HR, 0.686; 95% CI, 0.546-0.870; p = .0015 for P+E; OS: 4.0 mo for both arms, HR, 0.333; 95% CI, 0.264-0.422; p < .0001 for T+E; HR, 0.449; 95% CI, 0.353-0.576; p < .0001 for P+E). The VS-G population had higher OS than the VS-P population within Eastern Cooperative Oncology Group (ECOG) performance score (PS) categories. VS-G patients on the T+E arm had longer PFS, but not OS, than VS-G patients on the P+E arm (p = .0108). Among EGFR mutation-positive patients, those with VS-G status had a median OS more than twice that of any other group (OS: 31.6 mo for T+E and 22.8 mo for P+E), whereas VS-P patients had similar survival rates as VS-G, EGFR-wild type patients (OS: 13.7 mo for T+E and 6.5 mo for P+E).
Conclusion: In these analyses, VeriStrat showed a prognostic role within EGOC PS categories and regardless of treatment arm and EGFR status, suggesting that VeriStrat could be used to identify EGFR mutation-positive patients who will have a poor response to EGFR tyrosine kinase inhibitors.
Implications for practice: This study suggests that VeriStrat testing could enhance the prognostic role of performance status and smoking status and replicates findings from other trials that showed that the VeriStrat test identifies EGFR mutation-positive patients likely to have a poor response to EGFR tyrosine kinase inhibitors (TKIs). Although these findings should be confirmed in other populations, VeriStrat use could be considered in EGFR mutation-positive patients as an additional prognostic tool, and these results suggest that EGFR mutation-positive patients with VeriStrat "poor" classification could benefit from other therapeutic agents given in conjunction with TKI monotherapy.
摘要
背景。VeriStrat 检测为非小细胞肺癌 (NSCLC) 患者全线治疗的预后提供准确的预测。我们调查了 VeriStrat 在既往经治的晚期 NSCLC 患者中对比 Tivantinib 和厄洛替尼 (T+E) 与安慰剂和厄洛替尼 (P+E) 的 MARQUEE III 期试验的患者中的预测和预后作用。
方法。预处理996 名患者的血浆样本，并利用基质辅助激光解吸/电离飞行时间质谱法对这些血浆样本进行分析，以生成 VeriStrat 标签(好，VS‐G，或者差，VS‐P)。
结果。总体而言，厄洛替尼联合 Tivantinib，在总生存期 (OS) 和无进展生存期 (PFS) 方面未观察到显著益处。在不考虑治疗组的情况下，与分类为 VS‐P 的患者相比，分类为 VS‐G 的患者具有显著延长的 PFS(T+E 组为 3.8 个月，P+E 组为 2.0 个月)和 OS(T+E 组为 11.6 个月，P+E 组为 10.2 个月) [PFS:两组均为 1.9 个月，T+E 组:风险比 (HR)，0.584；95% 置信区间 (CI)，0.468–0.733；p < 0.000 1；P+E 组:HR，0.686；95% CI，0.546–0.870；p = 0.001 5；OS:两组均为 4.0 个月，T+E 组:HR，0.333；95% CI，0.264–0.422；p < 0.000 1；P+E 组:HR，0.449；95% CI，0.353–0.576；p < 0.000 1]。在东部协作肿瘤组 (ECOG) 体能评分 (PS) 类别内部，VS‐G 人群比 VS‐P 人群具有更长的 OS。T+E 组中的 VS‐G 患者比 P+E 组中的 VS‐G 患者具有更长的 PFS(而非 OS)(p = 0.010 8)。在 EGFR 突变阳性患者中，处于 VS‐G 状态的患者的中位 OS 是任何其他组的 2 倍以上(OS:T+E 组为 31.6 个月，P+E 组为 22.8 个月)，而 VS‐P 患者具有与 VS‐G、EGFR 野生型患者相似的生存率(OS:T+E 组为 13.7 个月，P+E 组为 6.5 个月)。
结论。在这些分析中，VeriStrat 在 EGOC PS 类别内部显示出预后作用，而且，在不考虑治疗组和 EGFR 状态的情况下，分析表明 VeriStrat 可用于识别对 EGFR 酪氨酸激酶抑制剂具有不良反应的 EGFR 突变阳性患者。
对临床实践的提示:本研究表明，VeriStrat 检测可以增强体能状态和吸烟状态的预后作用并重复其他试验的研究结果，这些研究结果表明 VeriStrat 检测可以识别可能对 EGFR 酪氨酸激酶抑制剂 (TKI) 具有不良反应的 EGFR 突变阳性患者。虽然应该在其他人群中确认这些研究结果，但是，在 EGFR 突变阳性患者中可以考虑将 VeriStrat 用作附加的预后工具，而且，这些结果表明具有 VeriStrat“差”类别的 EGFR 突变阳性患者可以从与 TKI 单药治疗联合使用的其他治疗制剂中获益。
Keywords: Biomarkers; Erlotinib; Non‐small cell lung cancer; Proteomics; Tivantinib.
© AlphaMed Press 2018.