Sequential PET/CT and pathological biomarker crosstalk predict response to PD-1 blockers alone or combined with sunitinib in propensity score-matched cohorts of cancer of unknown primary treatment

IntroductionThe efficacy of immune checkpoint inhibitors (ICIs), including toripalimab and pembrolizumab, has not been confirmed in the treatment of cancer of unknown primary (CUP), which has a very poor prognosis. Combined with anti-angiogenic therapies, ICIs are hypothesized to be effective in prolonging overall survival. The study aims to give evidence on the treatment effects of sunitinib combined with ICIs, find pathological biomarkers associated with changes in volumetric 18F FDG PET/CT parameters, and investigate inner associations among these markers associated with response on PET/CT.MethodsThe study recruited patients receiving combined treatment (ICIs + sunitinib), compared the effects of combined treatment with those of separate treatment and age-matched negative controls, and analyzed propensity score-matched (PSM) pairs. Markers associated with survival were identified, and their inner associations were tested using structural equation modeling.ResultsA total of 292 patients were enrolled in the final analysis, with 53 patients receiving combined treatment. Survival analysis demonstrated significantly prolonged survival in either combined or separate treatment, with the combined arm showing better response when PSM-paired using pre-treatment whole-body PET/CT parameters. The angiogenic markers KDR and VEGF mediate the PD-1 blockade impact on volumetric value changes in positive and negative manners.ConclusionThe anti-angiogenic agent sunitinib may potentiate PD-1 blockade by diminishing angiogenesis or its downstream effects. The combined separate treatment increased the survival of CUP patients, and the responses could be evaluated using volumetric PET/CT parameters.