e15091 Background: Early identification of patients likely to benefit from immune checkpoint inhibitors (ICIs) remains a major challenge across solid tumors. Circulating tumor DNA (ctDNA) kinetics have emerged as a promising noninvasive biomarker, yet results across studies are heterogeneous. We conducted a systematic review and meta-analysis to evaluate the prognostic and predictive value of early ctDNA reduction in patients receiving ICIs. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception through March 2025 following PRISMA guidelines. Studies evaluating early ctDNA dynamics (≤8 weeks after ICI initiation) in adult patients with solid tumors were included. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR). Random-effects models were used to pool hazard ratios (HRs) and odds ratios (ORs). Heterogeneity was assessed using I² statistics, and publication bias was evaluated with funnel plots and Egger’s test. Results: A total of 27 studies encompassing 3,842 patients across lung, melanoma, breast, gastrointestinal, and genitourinary malignancies met inclusion criteria. Early ctDNA reduction (defined as ≥50–90% decline or complete clearance, study-specific) was associated with significantly improved PFS (pooled HR 0.45; 95% CI 0.38–0.53; I² = 41%) and OS (pooled HR 0.40; 95% CI 0.32–0.49; I² = 36%). Patients demonstrating early ctDNA reduction had a markedly higher ORR (pooled OR 4.92; 95% CI 3.71–6.53; I² = 29%). Subgroup analyses showed consistent benefit across tumor types and ICI regimens. Early ctDNA dynamics outperformed baseline PD-L1 expression and tumor mutational burden in predicting treatment response. No significant publication bias was detected. Conclusions: Early ctDNA kinetics are a robust, tumor-agnostic biomarker associated with improved survival and treatment response in patients receiving ICIs. These findings support the integration of ctDNA monitoring into early treatment assessment and clinical trial design. Prospective trials are warranted to validate ctDNA-guided immunotherapy strategies.
Saravanan et al. (Thu,) studied this question.