Meta-analysis of ctDNA clearance as predictive biomarker of pCR to neoadjuvant ICIs for solid tumors

In patients with solid tumors undergoing neoadjuvant immune checkpoint inhibitor (ICI) therapy, identifying biomarkers to preoperatively predict pathologic complete response (pCR) could enahnce treatment modulation. Systematic review and meta-analysis of 13 phase 1b, 2, and 3 studies (380 patients) published before August 5, 2024, evaluated ctDNA clearance as biomarker predicting pCR. Overall, 38% of patients achieved pCR and 73% had ctDNA clearance before or at surgery. Pooled sensitivity was 0,98 whereas pooled specificity was 0.53. Significant heterogeneity was observed across studies. The authors conclude that lack of preoperative ctDNA clearance may identify patients unlikely to achieve pCR; whereas the confirmatory power of ctDNA clearance for achieving pCR is limited.