Pembrolizumab Erases ctDNA in Median 2 Cycles, Boosting 3-Year EFS to 92 % in dMMR/MSI-H Tumors

Phase II neoadjuvant trial NCT04082572 tracked 35 locally advanced dMMR/MSI-H cancers for 3 years: overall EFS/OS were 80% / 94%, but patients who cleared ctDNA after pembrolizumab hit 3-year EFS 92% and OS 100% versus 20% and 80% when ctDNA persisted (p < 0.001). Clearance was swift—9 of 14 ctDNA-positive patients turned negative after a median of just two cycles (mean 3.7; range 1–16). In colorectal cancer, ctDNA negativity predicted pCR (91 % vs 0 %) and enabled non-operative management with 2-year EFS 100 % versus 33 %. No new safety signals emerged on extended follow-up.

Early ctDNA clearance deliver an early, quantitative read-out that can de-risk immunotherapy duration and refine surgical decision-making in dMMR/MSI-H disease.