Abstract
3068 Background: We previously showed a correlation between circulating tumor DNA (ctDNA) dynamics and response to pembrolizumab in a cohort of mixed tumors treated in the INSPIRE study (Yang et al, ESMO 2019). We investigated the prognostic and predictive value of ctDNA dynamics in patients (pts) with VRT. Methods: Pts with VRT (HPV+ squamous cell carcinoma (SCC), EBER+ nasopharyngeal carcinoma (NPC) and MCPyV+ Merkel carcinoma (MC)) and a control cohort of non-VRT (HPV- head and neck SCC) treated with single-agent pembrolizumab were selected for the analysis. ctDNA was assayed at baseline and start of cycle 3 using a pt-specific amplicon-based NGS assay (Signatera). Samples were considered ctDNA positive if ≥2 of 16 pt-specific targets met the qualifying confidence score threshold. Whole exome sequencing (WES) performed in baseline tumor tissue; presence of HPV, EBV and MCPyV in tumor determined through bioinformatic analysis of WES data (VirusFinder, PMID23717618). Changes in tumor size (mm) and response data using RECIST 1.1 were collected. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Results: Twenty pts with VRT (HPV+ head and neck = 8, cervical = 2 and anal = 2 SCC; EBER+NPC = 2; MC = 6) and 11 pts with non-VRT were included. Median follow-up: 11 months (0,5-11). Treatment response: VRT 6 responders (CR + PR + SD > 18weeks) and 14 non-responders (SD < 18 weeks + PD); non-VRT 3 responders and 8 non-responders. Median OS and PFS for all pts were 10.61 and 3.2 months, respectively. No differences in PFS (p = 0.60) nor OS (p = 0.66) were observed among responders between VRT and non-VRT. Among non-responders, VRT had significantly higher OS but not PFS when compared to non-VRT (HR 0.30, p = 0.01 and HR 0.82 p = 0.62, respectively). VRT had quantitatively higher ctDNA at baseline vs non-VRT (Mean 7.9 vs 0.4 ng, p < 0.001). ΔctDNA (Change in ctDNA between baseline and cycle 3) strongly correlated with changes in tumor measurements and response by RECIST 1.1 (Spearman Rho = 0.75) and was associated with survival regardless of viral status (Table). Conclusions: ΔctDNA strongly correlated with changes in tumor response and survival in both VRT and non-VRT. Higher baseline ctDNA was found in VRT. Correlation with circulating viral DNA and radiomics analyses is on-going. [Table: see text]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have