Journal: NPJ precision oncology
This study evaluated a blood-based circulating tumor DNA (ctDNA) methylation assay as an early marker of response to pembrolizumab in patients with various metastatic solid tumors enrolled in a phase 2 trial (NCT02644369).
Using a tissue-agnostic, genome-wide cfDNA methylation platform (cfMeDIP-seq), the investigators measured ctDNA levels at baseline and again before cycle 3 of pembrolizumab.
A decrease in ctDNA over this interval was:
- Significantly associated with higher objective response rates
- Associated with higher clinical benefit rates
- Linked to longer progression-free survival (PFS) and overall survival (OS) in univariate analyses
In multivariable models adjusting for other clinical factors, the associations with objective response, clinical benefit, and PFS remained significant; the association with OS did not.
The key implication is that a commercial-grade, tissue-agnostic plasma cfDNA methylation assay can serve as an early, blood-only indicator of immunotherapy benefit, potentially enabling more timely treatment decisions for patients on pembrolizumab across multiple solid tumor types.