Nivolumab after cyclophosphamide and doxorubicin induction chemotherapy in previously treated patients with EGFR or ALK wild type non-squamous cell non-small cell lung cancer with less than 10% of PD-L1 expression
Research Square (Research Square)(2023)
Abstract
Abstract Purpose 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% PD-L1 expression. Methods Patients received four cycles of CA-IT (C,500 mg/m 2 and D, 50 mg/m 2 ) every 3weeks. Nivolumab was given 360 mg every 3 weeks from the second cycle. After 4 cycles of CA-IT, nivolumab 480 mg was administered every 4 weeks. We collected blood samples for next-generation sequencing, fluorescence-activated Cell Sorting (FACS) to characterize immune cells, and liquid chromatography-tandem mass spectrometry to identify potential biomarkers. Results A total of 22 patients were enrolled. The median progression-free and overall survivals were 2.4 months (95% CI, 1.3–3.5) and 11.6 months (95% CI, 5.3–18.0), respectively. Two patients with a partial response received nivolumab for 2 years without disease progression. FACS revealed the lowest ratio of myeloid-derived suppressor cells (MDSCs) to CD8 + T-cell throughout the treatment in 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 (TRFC), which mediates ferroptosis and phagocytosis, was higher in responders than in non-responders before treatment. Conclusions CA-IT did not improve nivolumab efficacy in NSQ-NSCLCs with low PD-L1 expression. However, CA-IT induced deceasing MDSC resulted in durable response. Higher baseline TRFC levels may predict favorable response to nivolumab in NSCLC with low PD-L1 expression. Trial Registration: NCT03808480
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Key words
doxorubicin induction chemotherapy,nivolumab,cyclophosphamide,cancer,non-squamous,non-small
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