Abstract
Simple SummaryProgrammed death-ligand 1 (PD-L1) expression in tumor tissue is a predictor for the efficacy of immune checkpoint inhibitors. We have previously reported that PD-L1 positive rate on circulating tumor cells (CTCs) in non-small cell lung cancer patients at baseline was correlated with response to nivolumab. Here, we sequentially evaluated PD-L1 expression on CTCs in 45 enrolled patients at baseline and week 4, 8, 12 and 24 or progressive disease (PD). The median of PD-L1-positive CTC number between baseline and week 8 were significantly different (p < 0.05), and progression-free survival was significantly longer in patients with ≥7.7% PD-L1 positivity rates (n = 8) than in those with <7.7% rates (n = 8; p < 0.01) at week 8. Our findings suggest that PD-L1 expression on CTCs during nivolumab treatment may be predictive of long-term efficacy.Although programmed death-ligand 1 (PD-L1) expression on tumor tissue is a validated predictive biomarker for a PD-1 pathway blockade in non-small cell lung cancer (NSCLC), longitudinal changes in its expression during treatment remains elusive. Circulating tumor cells (CTCs) are assumed to reflect the transition of characteristics of the primary tumor undergoing anticancer treatment. Here, we sequentially evaluated the PD-L1 expression on CTCs in NSCLC patients treated with nivolumab. Forty-five patients were enrolled, and CTCs were enriched from 3 mL of peripheral blood using a microcavity array system at baseline and weeks 4, 8, 12, and 24 or until progressive disease. The effective responses to therapy were compared between patients without progressive disease (PD) at week 8 (i.e., non-PD patients) and in those with PD between weeks 4 and 8 (PD patients) in terms of increased vs. decreased or equal CTC status at week 8 (for non-PD patients) or at the point of PD (for PD patients) compared to the baseline. Significantly more non-PD patients were classified as decreased or equal in number and proportion to PD-L1-positive CTCs among the detected CTCs (PD-L1 positivity rates) (p < 0.05). Moreover, progression-free survival was significantly longer in patients with ≥7.7% PD-L1 positivity rates (n = 8) than in those with <7.7% rates (n = 8; p < 0.01) at week 8. These results suggest the predictive significance of the early evaluation of PD-L1 expression on CTCs for maintaining the benefits from nivolumab treatment.
Highlights
The 5-year survival rate of patients with metastatic lung cancer after diagnosis was estimated to be only approximately 5% between 2008 and 2014 [1]
It has been clinically evaluated that the expression of progressive disease (PD)-ligand 1 (PD-L1) on tumor tissue is useful as a predictive biomarker fin response to the programmed death 1 (PD-1) pathway blockade; the incidences of patients who respond to the PD-1/PD-L1 blockade without PD-L1 expression in their tumor tissue indicate the insufficiency of this predictive technique [10,11,12]
We previously reported that PD-L1 positivity rate in Circulating tumor cells (CTCs) prior to nivolumab treatment is correlated with clinical efficacy, and the current study suggested the predictive significance of early evaluation of PD-L1 expression on CTCs during nivolumab treatment
Summary
The 5-year survival rate of patients with metastatic lung cancer after diagnosis was estimated to be only approximately 5% between 2008 and 2014 [1]. Molecular-targeted therapy has opened up the promising prospect for treating non-small cell lung cancer (NSCLC) and other solid tumors with effective clinical responses [2,3,4]. As one of these therapies, treatment with the programmed death 1 (PD-1)/PD-ligand 1 (PD-L1) pathway blockade for NSCLC patients dramatically improved tumor regression in approximately 20% of patients [5,6,7,8] and the 5-year survival in approximately 16% of patients [9]. The longitudinal evaluation of PD-L1 expression on tumor tissue through serial collection at multiple time points is needed; the repetitive acquisition of tumor specimens is difficult owing to a high invasiveness
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