Predictive Value of Soluble PD-1, PD-L1, VEGFA, CD40 Ligand and CD44 for Nivolumab Therapy in Advanced Non-Small Cell Lung Cancer: A Case-Control Study

• Published in: Cancers 2020-02, Vol.12 (2), p.473
• Main Authors: Tiako Meyo, Manuela, Jouinot, Anne, Giroux-Leprieur, Etienne, Fabre, Elizabeth, Wislez, Marie, Alifano, Marco, Leroy, Karen, Boudou-Rouquette, Pascaline, Tlemsani, Camille, Khoudour, Nihel, Arrondeau, Jennifer, Thomas-Schoemann, Audrey, Blons, Hélène, Mansuet-Lupo, Audrey, Damotte, Diane, Vidal, Michel, Goldwasser, François, Alexandre, Jérôme, Blanchet, Benoit
• Format: Article
• Language: English
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12020473

A large interindividual variability has been observed in anti Programmed cell Death 1 (anti-PD1) therapies efficacy. The aim of this study is to assess the correlation of soluble PD-1 (sPD-1), soluble Programmed cell Death Ligand 1 (sPD-L1), Vascular Endothelial Growth Factor A (VEGFA), soluble CD40 ligand (sCD40L) and soluble CD44 (sCD44), with survival in nivolumab-treated metastatic non-small cell lung cancer (NSCLC) patients. Plasma biomarkers were assayed at baseline and after two cycles of nivolumab. A cut-off of positivity for sPD-1, sPD-L1 and sCD40L expressions was defined as a plasma level above the lower limit of quantification. Baseline sPD-1 and sPD-L1 levels were subsequently analyzed in a control group of -mutated ( ) NSCLC patients. Association between survival and biomarkers was investigated using Cox proportional hazard regression model. Eighty-seven patients were included (51 nivolumab-treated patients, 36 in EGFR-mutated group). In nivolumab group, baseline sPD-1, sPD-L1 and sCD40L were positive for 15(29.4%), 27(52.9%) and 18(50%) patients, respectively. We defined a composite criteria (sCombo) corresponding to sPD-1 and/or sPD-L1 positivity for each patient. In nivolumab group, baseline sCombo positivity was associated with shorter median progression-free survival (PFS) (78 days 95%CI (55-109) vs. 658 days (222-not reached); HR: 4.12 (1.95-8.71), = 0.0002) and OS (HR: 3.99(1.63-9.80), = 0.003). In multivariate analysis, baseline sCombo independently correlated with PFS (HR: 2.66 (1.17-6.08), = 0.02) but not OS. In EGFR-mutated group, all patients were baseline sCombo positive; therefore this factor was not associated with survival. After two cycles of nivolumab, an increased or stable sPD-1 level independently correlated with longer PFS (HR: 0.49, 95%CI (0.30-0.80), = 0.004) and OS (HR: 0.39, 95%CI (0.21-0.71), = 0.002). VEGFA, sCD40L and sCD44 did not correlate with survival. We propose a composite biomarker using sPD-1and sPDL-1 to predict nivolumab efficacy in NSCLC patients. A larger validation study is warranted.