Prediction of long-term effect of anti-angiogenic therapy in lung cancer patients by monitoring early changes in circulating-tumor DNA (ctDNA)

<b>Introduction:</b> The efficacy of anti-angiogenic lung cancer therapy is relying on imaging techniques. Monitoring monitoring of minimal residual disease by detection and quantification of ctDNA opened a new ability to predict therapy response. This study was aimed at utility of a simple ctDNA detection assay for monitoring of therapy response to predict outcome. <b>Patients and Methods:</b> A total of 65 patients in Stage IV lung adenocarcinoma were prospectively enrolled into the study. Patients were treated by a combination of paclitaxel/carboplatin with bevacizumab. For each patient cytology tissue sample was subjected to test for a panel of mutations frequently detected in lung cancer. The mutations were then traced in plasma prior and during the therapy. <b>Results:</b> Somatic mutations were detected in 54% of tissue samples (35/65) with 12xTP53, 13 x KRAS, 8 x TP53+KRAS, 1 x BRAF and 1 x PIK3CA. Prior to 1st cycle ctDNA was detected in 18 of the 35 mutation-positive patients (51%), at 2nd cycle it was persisting in 10 patients. Kaplan-Meier analysis revealed the initial ctDNA associated with shorter PFS (150 vs. 507 days, p=0,0052). Furthermore at the start of the 2nd cycle ctDNA positivity predicted even significantly shorter PFS (61 vs. 460 days, p=0,0001). <b>Conclusion:</b> Status of ctDNA at the end of the first cycle is an independent predictor of non-targeted chemotherapy efficiacy. Patients without any signs of ctDNA or those with elimination of ctDNA at the end of the first cycle have a significantly longer PFS. Supported by project no. 17-30748A.