Circulating tumor DNA (ctDNA) dynamics associate with treatment response and radiological progression-free survival (rPFS): Analyses from a randomized phase II trial in metastatic castration-resistant prostate cancer (mCRPC).
Abstract Number : 5508
Abstract Type : Oral Abstract Session
Indication : Metastatic Castration Resistant Prostate Cancer
Intervention : Ipatasertib with or without abiraterone
Company : Roche
Technology : Small Molecule
Result:
Baseline (BL) ctDNA positivity correlated with radiological progression-free survival (rPFS; HR: 1.8 [95% CI 1.3-2.6], p , 0.01); this association with rPFS was maintained in a multivariate cox model with . 5 baseline clinical variables (HR: 1.6 [95% CI 1.1-2.4]; p = 0.011). Patients with a C3D1 reduction in ctDNA had superior rPFS compared to patients with a C3D1 increase in ctDNA (HR: 2 [95% CI 1.3-3.2], p , 0.01). The rate of ctDNA clearance at C3D1 was higher in the Ipatasertib 400mg arm compared to placebo (56.3% versus 24.4%, p , 0.01). We find that changes in ctDNA associated with best confirmed overall response (p = 0.024); CR patients had the greatest reduction in ctDNA (mean of -23.4%), followed by PR (-16.3%), then SD (-4.1%), and lastly PD patients (-1.3%). Changes in ctDNA levels correlated with SLD changes (rs = 0.289, p = 0.05), and also PSA changes (rs = 0.33, p , 0.01). Changes in ctDNA were associated with rPFS in a multivariate cox analysis that included PSA change (p , 0.01), as well as in a separate multivariate analysis that included SLD change (p , 0.01). Lastly, we explored CNVs and observed emerging resistance mutations in progression samples, including alterations in TP53, AR, FOXA, PTEN, and PI3K/AKT pathway genes
Conclusion:
ctDNA analyses may help (i) identify poorer prognosis disease at baseline, (ii) inform on treatment response (CR/PR/SD/PD) and radiological progression free survival (rPFS) in on-treatment (C3D1) samples, and (iii) can elucidate emerging resistance mechanisms at disease progression.
Commentary:
Combined ipatasertib and abiraterone improved rPFS in patients with mCRPC with PTEN loss. ctDNA analysis might help in better treatment response and disease progression.
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