Abstract 4107: Predictive value of soluble PD-1, PD-L1, VEGFA, CD40 ligand and CD44 for nivolumab efficacy in advanced non-small cell lung cancer
Authors: Meyo Manuela Tiako , Jouinot Anne , Giroux-Leprieur Etienne , Fabre Elizabeth , Boudou-Rouquette Pascaline , Bellesoeur Audrey , Arrondeau Jennifer , Blons Hélène , Mansuet-Lupo Audrey , Damotte Diane , Vidal Michel , Goldwasser François , Alexandre Jérôme , Blanchet Benoit 
Published: August 2019

Abstract
Context Anti-PD1 therapy nivolumab has been approved for the treatment of advanced non-small cell lung cancer (NSCLC). However, a large inter-individual variability in its efficacy has been observed. Thus, the search for reliable factors to predict anti-PD1 efficacy represents a major challenge, particularly in NSCLC patients. The aim of this prospective study was to assess the correlation of five immunity-related plasmatic biomarkers, soluble PD-1 (sPD-1), soluble PD-L1 (sPD-L1), VEGFA, soluble CD40L and soluble CD44, with survival in nivolumab-treated metastatic NSCLC patients.
Method This study included patients from the CERTIM prospective cohort (Immuno-modulatory Therapies Multidisciplinary Study group, Cochin Hospital, Paris, France), treated with nivolumab for a metastatic NSCLC between July 2015 and June 2017. Plasma levels of the five biomarkers were assayed at baseline and after two cycles of nivolumab using commercial ELISA kits. Due to their inconsistent expression, 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 (0.156ng/mL). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively.
Results Fitfty-one patients were included (43% female, median age 66 years old): 40 patients (78%) had an adenocarcinoma, and 35 (69%) received nivolumab as a second-line regimen. Median [interquartile range] follow-up was 804 days [553 - 1112]. Baseline sPD-1, sPD-L1 and sCD40L were positive for 15 (29.4%), 27 (52.9%) and 18 patients (50%), respectively. Baseline positivity of sPD-1 and sPD-L1 did not independently correlate with PFS and OS in multivariate analysis. We defined a composite criteria (sCombo) corresponding to the positivity of sPD-1 and/or sPD-L1 for each patient. Patients exhibiting baseline sCombo positivity experienced shorter PFS (median [95% confidence interval]: 78 days [55-109] vs. 658 days [222-not reached]; HR 4.12, 95%CI [1.95-8.71], p=0.0002) and OS (median [95% CI]: 367 days [167 - 501] vs. not reached [402 - not reached]; HR: 3.99, 95%CI [1.63-9.80], p=0.003). The multivariate analysis including clinical factors and tumor cell PD-L1 expression showed that positivity of baseline sCombo was independently associated with a shorter PFS (HR: 2.66, 95%CI [1.17-6.08], p=0.02) but not with OS (HR: 2.17,95%CI [0.86-5.45], p=0.10). An increased or stable sPD-1 level after two cycles of nivolumab independently correlated with longer PFS (HR: 0.23, 95%CI [0.09-0.62], p=0.004) and OS (HR: 0.16, 95%CI [0.05-0.52], p=0.002). VEGFA, sCD40L and sCD44 did not correlate with patients’ survival in this cohort.
Conclusion We propose a composite biomarker using soluble PD1 and soluble PDL1, predictive of nivolumab efficacy in NSCLC patients. A larger prospective validation study is warranted to confirm these results.
Citation Format: Manuela Tiako Meyo, Anne Jouinot, Etienne Giroux-Leprieur, Elizabeth Fabre, Pascaline Boudou-Rouquette, Audrey Bellesoeur, Jennifer Arrondeau, Hélène Blons, Audrey Mansuet-Lupo, Diane Damotte, Michel Vidal, François Goldwasser, Jérôme Alexandre, Benoit Blanchet. Predictive value of soluble PD-1, PD-L1, VEGFA, CD40 ligand and CD44 for nivolumab efficacy in advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4107.