Heterogeneity of circulating tumor cells (CTCs) in patients with recurrent small cell lung cancer (SCLC) treated with pazopanib

•Pazopanib is a small molecule with a tyrosine multikinase inhibitor activity.•CTCs detection could serve as a prognostic and predictive tool in SCLC.•Pazopanib effect on CTCs was an early event, and even after one treatment cycle.

ObjectivesTo investigate the effect of pazopanib on different CTCs subpopulations in patients with recurrent SCLC and evaluate their clinical relevance.MethodsPeripheral blood was obtained before the administration of pazopanib (n = 56 patients), after the first cycle (n = 35 patients) and at disease progression (n = 45 patients). CTCs were detected by CellSearch and double immunofluorescent staining using antibodies against the cytokeratins (CK), TTF-1, CD56 and VEGFR2.ResultsBefore treatment, CTCs could be detected in 50% of patients by CellSearch; phenotypic characterization of CTCs demonstrated that 50%, 46.6% and 27.6% of patients had CD45−/TTF1+, CD45−/CD56+ and TTF-1+/CD56+ CTCs, respectively. Additionally, 59% of CTCs were TTF-1+/VEGFR2+ and 53% CK+/VEGFR2+. One pazopanib cycle resulted to a significant decrease of the number of CTCs (CellSearch: p = 0.043) and CK+/VEGFR2+ cells (p = 0.027). At the time of PD, both the total number of CTCs (p = 0.027) and the number of the different subpopulations were significantly increased compared to post-1st cycle values; this increased CTCs number was associated with a significant increase of TTF-1+/VEGFR2+ (p = 0.028) and CK+/VEGFR2+ CTCs (p = 0.018). In multivariate analysis, only the number of CTCs as assessed by CellSearch after one treatment cycle was significantly associated with OS (HR: 0.21; p = 0.005).ConclusionsPazopanib has a significant effect on different subpopulations of CTCs in patients with relapsed SCLC; the detection of VEGFR2+ CTCs during treatment could be a surrogate marker associated with resistance to pazopanib.