Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan.
Thorac Cancer. 2018 Oct;9(10):1291-1299. doi: 10.1111/1759-7714.12838. Epub 2018 Aug 20.
Although phase III trials have shown improved overall and progression-free survival (PFS) using nivolumab compared to docetaxel in patients with non-small-cell lung cancer, the progressive disease ratio of nivolumab is higher than docetaxel. Furthermore, nonconventional response patterns of nivolumab make it difficult to determine the time point for nivolumab discontinuation. Therefore, a method to detect non-responders to nivolumab at an early time point is crucial. This retrospective study was conducted to identify immunological and nutritional markers, including neutrophil-to-lymphocyte ratios (NLR), which would predict the efficacy of nivolumab treatment. Because the expression of these markers fluctuates dramatically during treatment, repeat evaluation was performed.
We retrospectively investigated 30 patients with non-small-cell lung cancer who were treated with nivolumab. The stratified data of each marker obtained during four weeks after nivolumab treatment were evaluated by Cox proportional hazards regression to verify the differences in PFS.
One and four patients experienced progressive disease within two and four weeks, respectively. Therefore, 29 and 26 patients were analyzed two and four weeks after nivolumab administration, respectively. The results showed that the NLR after four weeks could predict PFS. The median PFS in 21 patients with NLR < 5 after four weeks of nivolumab administration was 95 days (95% confidence interval [CI] 50-NA), while the mPFS in five patients with NLR ≥ 5 was 10 days (95% CI 6-NA). NLR ≥ 5 showed a hazard ratio of 5.995 (95% CI 1.225-29.35).
Clarifying NLR four weeks after nivolumab administration may be useful to predict outcomes in nivolumab-treated patients.
尽管 III 期临床试验表明，与多西他赛相比，纳武利尤单抗可改善非小细胞肺癌患者的总生存期和无进展生存期（PFS），但纳武利尤单抗的疾病进展比例高于多西他赛。此外，纳武利尤单抗的非传统反应模式使得难以确定停止纳武利尤单抗的时间点。因此，及早检测纳武利尤单抗无应答者的方法至关重要。这项回顾性研究旨在确定包括中性粒细胞与淋巴细胞比值（NLR）在内的免疫和营养标志物，这些标志物可以预测纳武利尤单抗治疗的疗效。由于这些标志物在治疗过程中波动很大，因此进行了重复评估。
我们回顾性调查了 30 名接受纳武利尤单抗治疗的非小细胞肺癌患者。通过 Cox 比例风险回归分析评估纳武利尤单抗治疗后四周内各标志物的分层数据，以验证 PFS 的差异。
分别有 1 例和 4 例患者在 2 周和 4 周内出现疾病进展。因此，分别在纳武利尤单抗给药后 2 周和 4 周分析了 29 例和 26 例患者。结果表明，四周后 NLR 可预测 PFS。在四周后 NLR<5 的 21 例患者中，中位 PFS 为 95 天（95%置信区间 [CI] 50-N/A），而 NLR≥5 的 5 例患者的 mPFS 为 10 天（95% CI 6-N/A）。NLR≥5 显示危险比为 5.995（95% CI 1.225-29.35）。
在纳武利尤单抗治疗后四周明确 NLR 可能有助于预测纳武利尤单抗治疗患者的结局。
