期刊
JCO PRECISION ONCOLOGY
卷 6, 期 -, 页码 -出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1200/PO.22.00457
关键词
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类别
资金
- MD Anderson Cancer Center
- University of Maryland Greenebaum Cancer Center
- Genentech
- R43 NCI-NIH [R43CA206840]
- Defense Advanced Research Projects Agency (DARPA) [W911NF-14-C-0098]
This study found that blood-based monitoring of dynamic changes in PD-L1 in TACs can identify patients with rmNSCLC who may benefit from ICI therapy.
PURPOSE Current diagnosticmethods to determine programmed death 1 (PD-1) receptor and its ligand (PD-L1)/PD-1 immunotherapy (immune checkpoint inhibitor [ICI]) efficacy in recurrent or metastatic non-small-cell lung carcinoma (rmNSCLC) are imprecise. Although previously shown that patients with high tumor PD-L1 (>= 50%) demonstrate clinical benefit in the form of disease reduction and improved survival, patients with low PD-L1 (< 50%) sometimes benefit from treatment. Since the PD-L1/PD-1 pathway is dynamic, monitoring PD-L1 levels during treatment may be more accurate than a static baseline tumor biopsy; however, rebiopsying the primary or metastatic disease is rarely feasible. Liquid biopsies that measure the upregulation of PD-L1 on tumor-associated cells (TACs), ie, cancerassociated macrophage-like cells and circulating tumor cells, have been performed, but their predictive value for ICI therapy efficacy is unknown. MATERIALS AND METHODS We initiated a single-blind prospective study to evaluate TAC PD-L1 expression changes in rmNSCLC from blood samples before (T0) and after (T1) treatment with ICI (ICI, n = 41) or without ICI (no ICI, n = 41). Anonymized blood was filtered to isolate TACs, which were then quantified for high/low PD-L1 expression. Progression-free survival (PFS) or overall survival (OS) hazard ratios (HRs) were evaluated at 18 and 24 months by censored univariate analysis. RESULTS Increased TAC PD-L1 expression between T0 and T1 in patients who were not treated with ICI had no relationship with PFS or OS. However, increased TAC PD-L1 expression between T0 and T1 in patients treated with ICI had significantly better PFS (HR, 3.49; 95% CI, 1.5 to 8.3; P =.0091) and OS (HR, 3.058; 95% CI, 1.2 to 7.9; P =.0410). CONCLUSION Blood-based monitoring of dynamic changes in PD-L1 in TACs appears to identify patients with rmNSCLC who may benefit from ICI.
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