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  • N non small cell lung cancer Clin Lung Cancer

    2020-03-24

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    THORACIC
    Original Study
    Adjuvant Chemotherapy Increases Programmed Death-Ligand 1 (PD-L1) Expression in Nonesmall Cell Lung Cancer Recurrence r> Max Lacour,1 Stefanie Hiltbrunner,2 Seok-Yun Lee,2 Alex Soltermann,3 Elisabeth Jane Rushing,4 Davide Soldini,3 Walter Weder,1 Alessandra Curioni-Fontecedro2
    Abstract
    We sought to determine the effect of chemotherapy on programmed death-ligand 1 (PD-L1) LOXO-101 in non esmall-cell lung cancer and variability upon PD-L1 expression on initial tumor and recurrence. Our results suggest that chemotherapy might increase PD-L1 expression and demonstrate variability from primary tumor to recurrence.
    Background: Despite recent studies, the effect of chemotherapy on programmed death-ligand 1 (PD-L1) expression remains controversial. In this study, we investigated whether PD-L1 expression is affected by platinum-based chemotherapy. Furthermore, we evaluated correlation of PD-L1 expression with oncogenic driver alterations. Materials and Methods: We retrospectively evaluated changes in PD-L1 expression by immunohistochemical (IHC) analysis in resected specimens and in biopsies at nonesmall cell lung cancer recurrence LOXO-101 in patients receiving or not adjuvant chemotherapy after surgical resection. Four IHC score groups were defined: TC0 < 1%, T 1% and < 5%, TC2 5% and < 50%, and TC3 50%. Results: Thirty-six patients with adenocarcinoma were included. Twenty (56%) patients underwent adjuvant chemotherapy, and 16 (44%) patients did not receive adjuvant chemotherapy. PD-L1 expression was present in 10 (28%) of 36 initial tumor specimens. From patients receiving adjuvant chemotherapy, 7 (35%) of 20 tumor biopsies showed significant upregulation in PD-L1 expression at recurrence. In contrast, from patients with no adjuvant therapy, only 2 (12.5%) of 16 showed a change in PD-L1 expression. Six (17%) of 36 patients were PD-L1-negative in the primary tumor and turned positive at recurrence. KRAS mutation was present in 70% of patients expressing PD-L1. Conclusion: PD-L1 expression in nonesmall cell lung cancer can change from primary to recurrence, implicating the need for re-biopsy at recurrence. Moreover, chemotherapy might increase expression of PD-L1, supporting a combinatorial therapy with chemotherapy and anti-PD(L)1 treatment.
    Keywords: Checkpoint inhibitors, Chemotherapy, Immunotherapy, Non-small cell lung cancer, PD-L1
    Introduction
    The emerging field in cancer immunotherapy has revolutionized therapy strategy for nonesmall cell lung cancer (NSCLC);
    1Department of Thoracic Surgery 2Department of Medical Oncology and Hematology 3Institute of Surgical Pathology 4Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland
    Address for correspondence: Alessandra Curioni-Fontecedro, MD, PhD, Department
    of Medical Oncology and Hematology, University Hospital Zurich, Raemistrasse 100,
    8091 Zurich, Switzerland E-mail contact: [email protected]
    nevertheless, NSCLC remains one of the cancer types with the highest mortality rate worldwide and accounts for almost 80% of all lung cancers.1,2 Surgical resection remains the key component in operable early stage or locally advanced NSCLC followed or not by adjuvant chemotherapy.3 As the identification of common driver mutations in NSCLC, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has already been integrated in clinical guidelines as targeted drug therapy, recent advances in oncologic therapy have led to new therapeutic ap-proaches including immunotherapy targeting checkpoint inhibitors such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. PD-1 is a key immune-checkpoint molecule expressed by activated T-cells in order not to overshoot during an