Nicolas Guibert1, Myriam Delaunay2, Amélie Lusque3, Nadia Boubekeur4, Isabelle Rouquette5, Estelle Clermont5, Jean Mourlanette6, Sandrine Gouin6, Inge Dormoy6, Gilles Favre7, Julien Mazieres2, Anne Pradines4. 1. Thoracic Oncology Department, Larrey Hospital, University Hospital of Toulouse, France; Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; University of Toulouse III (Paul Sabatier), Toulouse, France. Electronic address: guibert.n@chu-toulouse.fr. 2. Thoracic Oncology Department, Larrey Hospital, University Hospital of Toulouse, France; Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; University of Toulouse III (Paul Sabatier), Toulouse, France. 3. Cellule Biostatistique, Bureau des Essais Cliniques, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France. 4. Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; Laboratoire de Biologie Médicale Oncologique, Institut Universitaire du Cancer de Toulouse, France. 5. Pathology Department, IUCT-Oncopole, Toulouse, France. 6. Thoracic Oncology Department, Larrey Hospital, University Hospital of Toulouse, France. 7. Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; Laboratoire de Biologie Médicale Oncologique, Institut Universitaire du Cancer de Toulouse, France; University of Toulouse III (Paul Sabatier), Toulouse, France.
Abstract
BACKGROUND: Inhibitors of the PD-1/PD-L1 immune checkpoint have become a standard of care in non-small cell lung cancer (NSCLC). Patient selection, currently based on PD-L1 expression on tumor tissue, is limited by its temporal and spatial heterogeneity. We hypothesized that liquid biopsy with PD-L1 analysis on circulating tumor cells (CTCs) might overcome this limitation. METHODS: Blood samples were prospectively collected from patients with advanced NSCLC before nivolumab treatment and at the time of progression. CTCs were isolated using a cell size-based technology. PD-L1 expression was assessed by immunofluorescence on CTCs and immunohistochemistry on tissue biopsies. RESULTS: 113 specimens from 96 patients were collected. Baseline PD-L1 expression could be assessed on 72% and 93% of tissue and CTC, respectively. CTCs were more frequently found to be PD-L1 positive than tissue (83% vs. 41%) and no correlation was observed between tissue and CTC PD-L1 expression (r = 0.04, p = 0.77). Pre-treatment high CTC number was associated with increased risk of death and progression (HR1.06, p = 0.03 for OS; HR1.05, p = 0.02 for PFS). The presence of pre-treatment PD-L1+CTC was not significantly correlated with outcomes but a higher baseline PD-L1+ CTC number (≥1%) was observed in the "non-responders" group (PFS <6 months) (p = 0.04) and PD-L1+CTC were seen in all patients at progression. CONCLUSION: Assessment of PD-L1 expression in CTCs is feasible and CTCs are more often positive than in tissue. Pre-treatment PD-L1+CTCs are associated with bad prognosis in patients treated with PD-1 inhibitors.
BACKGROUND: Inhibitors of the PD-1/PD-L1 immune checkpoint have become a standard of care in non-small cell lung cancer (NSCLC). Patient selection, currently based on PD-L1 expression on tumor tissue, is limited by its temporal and spatial heterogeneity. We hypothesized that liquid biopsy with PD-L1 analysis on circulating tumor cells (CTCs) might overcome this limitation. METHODS: Blood samples were prospectively collected from patients with advanced NSCLC before nivolumab treatment and at the time of progression. CTCs were isolated using a cell size-based technology. PD-L1 expression was assessed by immunofluorescence on CTCs and immunohistochemistry on tissue biopsies. RESULTS: 113 specimens from 96 patients were collected. Baseline PD-L1 expression could be assessed on 72% and 93% of tissue and CTC, respectively. CTCs were more frequently found to be PD-L1 positive than tissue (83% vs. 41%) and no correlation was observed between tissue and CTC PD-L1 expression (r = 0.04, p = 0.77). Pre-treatment high CTC number was associated with increased risk of death and progression (HR1.06, p = 0.03 for OS; HR1.05, p = 0.02 for PFS). The presence of pre-treatment PD-L1+CTC was not significantly correlated with outcomes but a higher baseline PD-L1+ CTC number (≥1%) was observed in the "non-responders" group (PFS <6 months) (p = 0.04) and PD-L1+CTC were seen in all patients at progression. CONCLUSION: Assessment of PD-L1 expression in CTCs is feasible and CTCs are more often positive than in tissue. Pre-treatment PD-L1+CTCs are associated with bad prognosis in patients treated with PD-1 inhibitors.
Authors: Elena María Brozos-Vázquez; Roberto Díaz-Peña; Jorge García-González; Luis León-Mateos; Patricia Mondelo-Macía; María Peña-Chilet; Rafael López-López Journal: Cancer Immunol Immunother Date: 2020-10-28 Impact factor: 6.968
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675