RNA-based biomarker signatures in plasma as an independent predictor of outcome to chemotherapy in lung, colon, and breast cancers: Correlation of relative PD-L1 expression with immunotherapy outcomes.

Abstract

e14567 Background: Levels of cell-free circulating RNA (cfRNA) in cancer patients (pts) indicate tumor gene expressions and thus may provide a means, not only of evaluating response, but also for monitoring and predicting outcome to therapy. Methods: Blood was drawn every 6-8 weeks from pts undergoing various treatments (tx). CfRNA was extracted from resulting plasma and generated random-primed cDNA. Total cfRNA was quantitated by qPCR of β-actin, and correlated with pts response (CR/PR/SD/PD) determined by CT scans. Changes in PD-L1 expression were used to monitor response to immunotherapy in lung cancer pts. 125 pts (50 lung, 51 breast, 24 colon) were enrolled. Among the three tumor types, a total of 84 pts completed 1-3 lines of tx with an average of 5 blood draws per pt. Results: Changes in total levels of cfRNA over time correlated with pts outcomes in all three tumor types and were independent of the specific therapies. Increasing (INC) levels of cfRNA were predictive of disease progression and decreasing (DEC) levels with benefit from therapy, with an overall concordance of 81% (68/84 pts). Changes in relative PD-L1 expression were associated with immunotherapy outcomes in lung cancer (INC associated with progression, DEC associated with benefit). Lung: There was a 79% (23/29) concordance between changes in cfRNA levels and pts response. Changes in relative PD-L1 expression were predictive of outcome to immunotherapy in 9/10 pts. Breast: There was an 83% (30/36) concordance between cfRNA levels and pts response. Colon: There was a 79% (15/19) concordance between cfRNA levels and pts response. Conclusions: A noteworthy concordance was observed between clinical response and changes in cfRNA levels in lung, breast and colon cancer pts, independent of chemotherapy regimen. Changes in relative PD-L1 gene expression correlated specifically with outcome to immunotherapy (90%). We conclude that changing cfRNA levels can indicate tx response, and PD- L1 could be used to monitor response to immunotherapy.