105P - Plasma ctDNA dynamics as clinical response biomarker for NSCLC: A systematic review and meta-analysis

Background

Predicting early treatment response in patients with advanced non-small cell lung cancer (NSCLC) is challenging. Longitudinal assessment of circulating tumor DNA (ctDNA) can track tumor response to immune checkpoint blockade (ICB) and correlates with treatment outcomes in various tumors. This meta-analysis evaluates whether ctDNA clearance or decrease (molecular response) correlates with survival outcomes across diverse therapeutic modalities in NSCLC.

Methods

We systematically searched the MEDLINE, EMBASE, and Cochrane databases until April 2024 to identify studies evaluating the impact of ctDNA kinetics on survival outcomes in non-curative NSCLC settings. Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were calculated using a random effects model. Inter-study heterogeneity was evaluated with I2 statistics.

Results

We included 31 out of 3076 studies, encompassing 2,875 NSCLC patients undergoing systemic therapies, including targeted therapy (TT), ICB and chemotherapy. The pooled analysis revealed that patients exhibiting molecular response compared with non-responders had improved PFS (HR: 0.35[0.27,0.44], 95% CI, I² = 80%, P < 0.01) and OS (HR: 0.34 [0.28, 0.42], 95% CI, I² = 38%, P < 0.01). ctDNA decrease led to improvement in both PFS (HR: 0.48 [0.35, 0.66], I² = 79%, P < 0.01) and OS (HR: 0.38 [0.31, 0.47], I² = 0%, P < 0.01). ctDNA clearance led to even greater improvements in PFS (HR: 0.31 [0.21, 0.45], 95% CI, I² = 70%, P < 0.01) and OS (HR: 0.31 [0.20, 0.47], 95% CI, I² = 59%, P < 0.01) vs non-clearance. EGFR-mutant NSCLC patients who exhibited clearance of EGFR mutant clones in ctDNA demonstrated benefits in PFS (HR: 0.30 [0.20, 0.45], 95% CI, I² = 26%, P < 0.01) and OS (HR: 0.31 [0.19, 0.50], 95% CI, I² = 0%, P < 0.01). An increase in PFS was observed in patients with ctDNA decrease or clearance undergoing TT (HR: 0.41 [0.28, 0.58], 95% CI, I² = 41%, P < 0.01) and ICB (HR: 0.39 [0.32, 0.48], 95% CI, I² = 0%, P < 0.01).

Conclusions

Our results suggest that ctDNA dynamics predict survival outcomes in patients with NSCLC across diverse therapeutic modalities and merit further investigation as a surrogate endpoint in clinical trials and potentially in the drug approval process.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.