ASCO GU 2017: Association of changes in circulating cell-free plasma DNA and circulating tumor cells during treatment with clinical outcome from Olaparib in CRPC: exploratory analyses from the TOPARP-A trial

Orlando, Florida USA ( Validation and clinical qualification of better response biomarkers are needed to optimize treatment decision in CRPC. Nowadays, guidelines recommend waiting 12 weeks before stoping treatment due to lack of affect or even longer in the case of bone metastases where a confirmatory bone scan is recommended prior to treatment discontinuation.

It is known that CTC enumeration has a prognostic value in CRPC. 5 cells per 7.5ml cutoff has been associated with treatment success for different treatment modalities. 30% decline in CTC count during taxane or abiraterone treatment conferred an overall survival benefit. Circulating free DNA (cfDNA) can be isolated from plasma samples and permit study of tumor genomic material. CfDNA may serve as a treatment response marker. The aim of this study was to study CTC numbers and cfDNA levels association with treatment outcome in mCRPC patients treated with olaparib (PARP inhibitor). TOPARP-A is an open label phase 2 study of olaparib in these patients. CTC's were enumerated at baseline, 4 and 8 weeks of therapy (PO 400 mg BID). CfDNA was expressed as ng/ml of plasma. Radiologic progression free survival (rPFS) and overall survival (OS) were the main outcome of the trial. CTC count was dichotomized to <5 or >5 CTC's/7.5 ml. CfDNA change was evaluated as change from base line and as > 30% or 50% decline.

CfDNA after 4 weeks of olaparib decreased in the majority of patients. By week 8, the majority of non responders had rising cfDNA while in responders, cfDNA levels remained low. CTC conversion from low to high as early as 4 weeks of therapy was associated with rPFS and OS. Same association was seen with cfDNA decline.

The authors concluded that decrease in CTC counts and cfDNA were associated with improved outcomes from olaparib. Patients who benefit from olaparib can be identified as early as after 4 weeks of treatment.

Presenter: Joaquin Mateo,The institute of cancer research, UK

Written By: Miki Haifler, MD, M.Sc, Fox Chase Cancer Center

at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA