Response to PD-1 Blockers Alone or Combined with Anlotinib in Treatment of Anaplastic and Poorly Differentiated Thyroid Carcinoma : A Real-world Study to Identify Best-benefited Patients

Abstract BackgroundAnaplastic and poorly differentiated thyroid carcinoma (ATC/PDTC) have poor survival outcomes. Mono-therapy with either immuno-therapy or tyrosine kinase blockers (TKI) is sparsely reported and seems not to significantly affect prognosis or survival. We sought to testify whether combined therapies have a better outcome in real-world settings. Pathological plus PET/CT volumetric biomarkers were analyzed to find crosstalk associated with response.MethodsPatients receiving PD-1 blockers alone or combined with anlotinib were recruited to undergo sequential PET/CT scanning. Propensity score-matched analysis was carried out for comparison of treatment outcomes. Structure equation modeling was carried out to investigate the crosstalk among sensitive biomarkers. A nomogram was developed and validated using the patients in the same centers.ResultsA total of 69 patients received either combined or mono-therapy with a clinical benefit rate of 88.41% (61 / 69) and tolerable adverse events, with a mean survival time of 14.64 months. The mean survival time of the combined therapy group was 15.67 months. The mean improvement of total lesion glycolysis (TLG) for the combined group was 120.07 (29.42% improved from baseline). Angiogenic marker VEGFR, FGFR, and VEGF mediate the PD-1 blockade impact on TLG improvement.ConclusionAnti-angiogenic agents anlotinib could potentiate PD-1 blockade by diminishing angiogenesis or its downstream effects. The combined treatment increased survival and responses could be better evaluated by volumetric PET/CT parameters. Pathological biomarker expression levels were associated with TLG improvement in combined treatment.