Nivolumab after Induction Chemotherapy in Previously Treated Non-Small-Cell Lung Cancer Patients with Low PD-L1 Expression

• Published in: Cancers 2023-09, Vol.15 (18), p.4460
• Main Authors: Ahn, Beung-Chul, Park, Charny, Lee, Sang-Jin, Hong, Sehwa, Hwang, Ji-Eun, Kwon, Kyoungsuk, Kim, Jin Young, Kim, Kyung-Hee, Kim, Hyae Young, Lee, Geon Kook, Lee, Youngjoo, Han, Ji-Youn
• Format: Article
• Language: English
• Subjects: Anthracyclines; Apoptosis; Cancer; Cancer therapies; Care and treatment; CD8 antigen; Chemotherapy; Cyclophosphamide; Cytotoxicity; Death; Development and progression; Ethylenediaminetetraacetic acid; Extracellular matrix; Flow cytometry; Immune checkpoint inhibitors; Immune response; Immunomodulation; Induction therapy; Ions; Kinases; Ligands; Lung cancer; Lung cancer, Non-small cell; Lung diseases; Lymphocytes T; Medical prognosis; Non-small cell lung carcinoma; Oncology, Experimental; PD-L1 protein; Peptides; Protein folding; Proteins; Proteomics; Scientific equipment and supplies industry; Small cell lung carcinoma; Suppressor cells; T cells; Tomography; Transferrins; Tumor necrosis factor-TNF; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15184460

This study aimed to investigate whether cyclophosphamide (C) and adriamycin (A) induction therapy (IT) prior to nivolumab could enhance the efficacy of nivolumab in previously treated patients with non-squamous (NSQ) non-small-cell lung cancer (NSCLC) with less than 10% programmed death-ligand 1 (PD-L1) expression. Twenty-two enrolled patients received four cycles of CA-IT every 3 weeks. Nivolumab was given 360 mg every 3 weeks from the second cycle and 480 mg every 4 weeks after four cycles of CA-IT. The median progression-free survival (PFS) and overall survival (OS) were 2.4 months and 11.6 months, respectively. Fluorescence-activated cell sorting revealed the lowest ratio of myeloid-derived suppressor cells (MDSCs) to CD8+T-cells in the responders. Proteomic analysis identified a consistent upregulation of extracellular matrix-receptor interactions and phagosome pathways in the responders. Among the differentially expressed proteins, the transferrin receptor protein (TFRC) was higher in the responders before treatment (fold change > 1.2). TFRC validation with an independent cohort showed the prognostic significance of either OS or PFS in patients with low PD-L1 expression. In summary, CA-IT did not improve nivolumab efficacy in NSQ-NSCLCs with low PD-L1 expression; however, it induced decreasing MDSC, resulting in a durable response. Higher baseline TFRC levels predicted a favorable response to nivolumab in NSCLC with low PD-L1 expression.