纳武单抗(nivolumab )是靶向PD-1的单克隆抗体，用于二线治疗转移性非小细胞肺癌患者，而且20%的患者会从中获益。通过IHC方法对PD-1的配体PD-L1进行评估可以得到更好的结果。然而 ，目前为止仍缺乏有效预测的标志物。

        研究人员纳入了来自于4个不同机构的115例IV期非小细胞肺癌(42例鳞状细胞癌，73例腺癌)患者。在至少经过一线铂类药物化疗后，对这些患者给予纳武单抗 (3 mg/kg IV Q2W) 治疗。一线化疗的效果和对于纳武单抗治疗的反应有CT片进行诊断。用Chi2和Cox分析一线化疗与无进展生存期(PFS)、OS或纳武单抗相应之间的关系。

        研究结果表明，46例(40%)，44例(38%)和25例(22%)患者在一线铂类化疗时发生了PR，SD和PD。25例(22%)，34例(29.5%)，56例(48.5%)患者在接受纳武单抗治疗时发生了PR，SD和PD。从化疗中获益的59.5% (53/89)患者(SD+PR)在同样会在纳武单抗的治疗过程中收益。而只有20%的PD患者会在纳武单抗的后续治疗中产生获益(Chi2检验 p = 0.002)。一线双联化疗的类型并不应下个纳武单抗治疗的响应率。Cox单因素和多变量模型分析发现尽管年龄、组织学和形态学的改变各异，从化疗中获益的患者在接受纳武单抗治疗时PFS(P = 0.002)(一线化疗后PR，SD，PD患者的nivolumab方案中位PFS为4.9,3.3和1.8个月)的生存期得到改善。同时，总生存期OS(P = 0.03)也得到了改善。

        研究结论认为，对一线化疗的反应可能是NSCLC患者接受纳武单抗治疗预测PFS和OS良好的生物标志物。

        编号#3026

        摘要原文：

        Author(s): Coureche Guillaume Kaderbhai, Corentin Richard, Jean david Fumet, Anne Aarnink, Sandra Ortiz-Cuaran, Maurice Perol, Pascal Foucher, Bruno P. Coudert, Laure Favier, Aurelie Lagrange, Emeric Limagne, Paul Hofman, Pierre Saintigny, Francois Ghiringhelli; Centre Georges-François Leclerc, Dijon, France; CGFL, Dijon, France; INSERM U1052, CNRS UMR 5286, Cancer Research Center of Lyon, Université de Lyon, Centre Léon Bérard, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon, Lyon, France; Department of Thoracic Oncology, Centre Léon Bérard, Lyon, France; Dijon University Hospital, Dijon, France; Center Georges-François Leclerc, Dijon, France; Centre Georges Francois Leclerc, Dijon, France; Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, FHU OncoAge, University Côte d'Azur, Nice, France

        Abstract:

        Background Nivolumab is a monoclonal antibody, targeting PD-1 receptor and demonstrating durable clinical benefit in 20% of metastatic NSCLC patients in second and further treatment lines. The expression of one of the PD-1 ligand, PD-L1 assessed by IHC is associated with better outcome. However, robust predictive markers of efficacy are lacking. Methods 115 pts with stage IV NSCLC (42 squamous, 73 adenocarcinoma) were included in this retrospective study in 4 different institutions. They received nivolumab (3 mg/kg IV Q2W) after at least one line of systemic platinum-based chemotherapy. Response to first line chemotherapy and to nivolumab (RECIST 1.1) was determined on CT scan by two physicians. Association between best response to first-line regimen and PFS, OS or response to nivolumab was determined using both Chi2 and Cox analysis. 46 (40%), 44 (38%) and 25 (22%) patients experimented PR, SD and PD to first-line platinum-based chemotherapy. 25 (22%), 34 (29.5%), 56 (48.5%) experimented PR, SD and PD to nivolumab. 59.5% (53/89) of patients who experimented clinical benefit (SD+PR) to first-line also experimented clinical benefit to nivolumab while only 20% (5/25) of patients with PD as best response to chemotherapy experimented clinical benefit to nivolumab (Chi2 test p = 0.002). The type of first-line doublet chemotherapy did not influence the response rate to nivolumab. Cox uni and multivariate models included age, histology and performance status underlined that patients with clinical benefit from chemotherapy had improved PFS with nivolumab (P = 0.002) (median PFS on nivolumab regimen of 4.9, 3.3 and 1.8 months for patients with PR, SD and PD to first-line, respectively). Similar results were obtained for OS (P = 0.03). Conclusions Our data suggest that response to first-line chemotherapy may be a good surrogate marker of response, PFS and OS to post-platinum nivolumab in metastatic NSCLC.