納武單抗(nivolumab )是靶向PD-1的單克隆抗體，用於二線治療轉移性非小細胞肺癌患者，而且20%的患者會從中獲益。通過IHC方法對PD-1的配體PD-L1進行評估可以得到更好的結果。然而 ，目前為止仍缺乏有效預測的標誌物。
研究人員納入了來自於4個不同機構的115例IV期非小細胞肺癌(42例鱗狀細胞癌，73例腺癌)患者。在至少經過一線鉑類藥物化療後，對這些患者給予納武單抗 (3 mg/kg IV Q2W) 治療。一線化療的效果和對於納武單抗治療的反應有CT片進行診斷。用Chi2和Cox分析一線化療與無進展生存期(PFS)、OS或納武單抗相應之間的關係。
研究結果表明，46例(40%)，44例(38%)和25例(22%)患者在一線鉑類化療時發生了PR，SD和PD。25例(22%)，34例(29.5%)，56例(48.5%)患者在接受納武單抗治療時發生了PR，SD和PD。從化療中獲益的59.5% (53/89)患者(SD+PR)在同樣會在納武單抗的治療過程中收益。而隻有20%的PD患者會在納武單抗的後續治療中產生獲益(Chi2檢驗 p = 0.002)。一線雙聯化療的類型並不應下個納武單抗治療的響應率。Cox單因素和多變量模型分析發現盡管年齡、組織學和形態學的改變各異，從化療中獲益的患者在接受納武單抗治療時PFS(P = 0.002)(一線化療後PR，SD，PD患者的nivolumab方案中位PFS為4.9,3.3和1.8個月)的生存期得到改善。同時，總生存期OS(P = 0.03)也得到了改善。
研究結論認為，對一線化療的反應可能是NSCLC患者接受納武單抗治療預測PFS和OS良好的生物標誌物。
編號#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.
