PD-L1 Expression on Circulating Tumor Cells Predicts Prognosis in OMNIVORE Trial

Even with the latest therapeutic progressions for individuals with renal cell carcinoma (RCC) utilizing immunotherapies, either alone or in conjunction with VEGF tyrosine kinase inhibitors, there is a shortage of biomarkers to predict patient benefit and assess mechanisms of resistance. The acknowledged heterogeneity of renal cell carcinoma (RCC) may account for the restricted use of biomarker examination on biopsies from a single site. The circumstance above has sparked significant enthusiasm for employing liquid biopsy to obtain neoplastic cells to assess response and resistance mechanisms. Considering the increasing utilization of immunotherapy (IO) among patients diagnosed with RCC, and the potential of their companion diagnostics in various disease contexts, researchers assessed the efficacy of liquid biopsy quantification of PD-L1 in forecasting patient reaction to IO in the OMNIVORE clinical trial, NCT03203473. The subjects under study were administered nivolumab monotherapy and subjected to radiographic scans on the third day of the clinical trial. The subsequent scans were conducted to validate complete response (CR) or partial response (PR), which were defined as “response.”

Patients who exhibited a response were subjected to observation, whereas those who did not respond were shifted to the arm of dual therapy involving nivolumab and ipilimumab. The quantification of PD-L1 and HLA I expression was performed on circulating tumor cells (CTCs) utilizing Exclusion-Based Sample Preparation (ESP) methodology. The utilization of single-cell protein analysis on circulating tumor cells (CTCs) allowed for the computation of summary statistics, such as the mean expression of PD-L1 and HLA I across all CTCs, the number of CTCs classified as positive for PD-L1 or HLA I, and the occurrence of CTCs exhibiting positive or negative expression. ROC curves were utilized to assess the diagnostic sensitivity and specificity of various CTC summary statistics in a cohort of 30 patients with assessable matched baseline and arm assignment data. The Kaplan-Meier curve was evaluated on the summary statistic that was determined to possess the highest clinical significance. The ROC curve analysis has determined that the metric “number of programmed death-ligand 1 positive circulating tumor cells” at arm assignment has the highest clinical value (AUC 0.8) compared to all other circulating tumor cell summary statistics evaluated.

At a cutoff of 2.5 PD-L1+ CTCs / 7.5 mL, the diagnostic sensitivity/specificity is 88/60%. The survival analysis indicated that patients exhibiting a lower count of programmed death-ligand 1 positive circulating tumor cells experienced a more extended and sustained response (68 weeks compared to 16 weeks, HR 2.9) to administering nivolumab as a single therapeutic agent. The findings indicated that the quantity of PD-L1+ circulating tumor cells can be a biomarker for evaluating treatment response. This biomarker could help determine treatment plans and explore new combination therapies for patients with unfavorable prognoses. The biomarker mentioned above is currently being evaluated in various prospective clinical trials to investigate its usefulness further.

Source:https://www.abstractsonline.com/pp8/#!/10517/presentation/17576

Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03203473

Rory M. Bade, Jennifer L. Schehr, Matthew C. Mannino, Matthew L. Bootsma, Hamid Emamekhoo, Shuang G. Zhao, Toni K. Choueiri, Sabina Signoretti, Rana R. McKay, Joshua M. Lang/Identification of PD-L1 expression on circulating tumor cells as a prognostic indicator in a prospective clinical trial, OMNIVORE/(2020). Abstractsonline.com. https://www.abstractsonline.com/pp8/#

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