Table 5.
Selective studies investigating the predictive role of PD-L1-positive CTCs in advanced NSCLC patients in treatment with ICIs. Abbreviations: NSCLC, non-small cell lung cancer; CTC, circulating cancer cell; ICI, immune checkpoint inhibitor; PD-L1, programmed cell death ligand 1; PD, progressive disease; ISET, isolation by size of tumour cells; PFS, progression-free survival; OS, overall survival; pts, patients; Nivo, nivolumab; EMT, epithelial–mesenchymal transition; MTV, metabolic tumour volume; MCA, automated microcavity array; PR, partial response; NR, not reached; Pembro, pembrolizumab.
| Study | Analysis Time-Point | Patients (n) |
Therapeutic Approach | Detection Method | Predictive Relevance |
|---|---|---|---|---|---|
| Nicolazzo et al. [114] | At baseline and at 3 and 6 months | 24 | Nivo | CellSearch | At 6 months of treatment, patients with PD-L1-negative CTCs all obtained a clinical benefit, while patients with PD-L1(+) CTCs all experienced PD |
| Guibert et al. [67] | At baseline and at PD | 96 | Nivo | ISET | The presence of PD-L1 + CTCs at baseline was not significantly correlated with PFS (p = 0.55) or OS (p = 0.89), but a higher baseline PD-L1+ CTC number (≥1%) was observed in the “non-responders” group (PFS < 6 mo.) (p = 0.04), and PD-L1 + CTC were seen in all patients at PD |
| Raimondi et al. [115] | At baseline | 15 | Nivo | ScreenCell Cyto | Coexpression of PD-L1 and EMT markers might represent a possible molecular background for immune escape in pts with NSCLC under treatment with Nivo |
| Spiliotaki et al. [116] | At baseline, post-1st cycle, post-3rd cycle, and at primary resistance | 47 | Pembro | Ficoll density gradient centrifugation | PD-L1+ Pts with Ki67+ CTCs > 30% before treatment had a shorter PFS compared to those with a Ki67 ≤ 30% (2 mo. vs. NR, respectively, p < 0.001); OS was shorter in PD-L1+ patients harbouring Ki67+ CTCs compared to those not presenting (median OS: 11.8 mo. vs. 33.1 mo., respectively; p = 0.035). In sequential samples of patients with a durable benefit, a low Ki67 index was observed |
| Castello et al. [117] | At baseline and 8 weeks after ICI initiation | 35 | ICIs | ISET | The combination of mean CTC and median MTV at 8 weeks was associated with PFS (p < 0.001) and OS (p = 0.024). CTC number is modulated by previous treatments and correlates with metabolic response during ICI |
| Ikeda et al. [118] | At the baseline and weeks 4, 8, 12, and 24 | 45 | Nivo | MCA system | The PD-L1 positivity rate in CTCs at week 8 or immediate increase in the number of CTCs prior to achieving PR and the decrease thereafter were significantly correlated with response to Nivo |
| Zhou et al. [66] | At baseline | 139 | ICIs | Cyttel method | No correlation between PD-L1 expression to CTCs and tumour tissues. Pts with PD-L1 detected on CTCs or tissue achieved significantly prolonged PFS compared to those without PD-L1 (5.6 mo. vs. 1.4 mo., log-rank p = 0.032) |
| Janning et al. [119] | At baseline, during treatment, and at PD | 127 | ICIs | Parsortix system | The percentage of PD-L1+ CTCs did not correlate with the percentage of PD-L1+ in biopsies (p =0.179). Upon PD, all pts showed an increase in PD-L1+ CTCs, while no change or a decrease in PD-L1+ CTCs was observed in responding patients (p = 0.001). |