De Bono #AACR19 But in early-stage in PrCa: Very few CTCs, struggling 'with this for over a decade'. CTC counts are used as co-primary endpt
De Bono #AACR19 Changes in CTC w/Rx in PhIII: pt-level surrogacy demonstrated in PrCa. Counts embedded in multiple trials.
De Bono #AACR19 CTC counts 'highly prognostic' (br, pros, CRC, SCLC). No doubt - changes in CTC counts post-Rx assoc'd w/resp.
De Bono #AACR19 CTCs "are making a comeback". Where we are now: assays 'highly reproducible', regulatory clearance obtained.
De Bono #AACR19 Shows fig from '18 Cell https://t.co/kig8IjorbL
De Bono #AACR19 Shows during Rx response (flat copy number); at progression copy number looks very similar. aCGH da… https://t.co/BneQgxwFKU
De Bono #AACR19 Different sites have different mutations. Shows unpubl data, low-pass WGS of mCRPC: defining CNV. A… https://t.co/CGgk4T6R7H
De Bono #AACR19 Other markers - miRNA and mRNA are 'attracting attention but need further validation'. Mehra '18 Go… https://t.co/VikHj6lohf
De Bono #AACR19 Whole-blood apheresis: CTC counts do not fall - continuously produced. Methods - targeted NGS, ddPCR, WES, low-pass WGS.
De Bono #AACR19 Lack of proof for clin utility. Onto circulating biomarkers: cfDNA conc. can be prognostic; cfDNA c… https://t.co/Kbb7Lh18BI
De Bono #AACR19 Plenty of reasons of failure for validation and qualification; reproducibility crises of 11%. Insuf… https://t.co/Ql8iqwvTTm
De Bono #AACR19 Clinical qualification: for many biomarkers 'we have not done that' - like w/AR-V7 we have not done… https://t.co/EiD115MC8S
De Bono #AACR19 Repro: intra-lab, inter-lab, biological variability across time. Diurnal rhythm, fasting/fed, exercise.
De Bono #AACR19 The devil in the details with analytical validation: LoD, FNs, continuous variables are preferred o… https://t.co/ZxdTeRE1Fn
De Bono #AACR19 If good prognosis: you have a problem; you'll need large randomized trials... The process of obtain… https://t.co/EzjgrXAvsN
De Bono #AACR19 PTEN loss: studying a PhIII Roche drug: AKT-blockade. Both prognostic and predictive: if prog of po… https://t.co/cy2BXO4lgV
De Bono #AACR19 Pre-Rx: can be difficult to dissect the prognostic from the prognostic AND predictive. AR7 splice v… https://t.co/MMxBMJjjiZ
De Bono #AACR19 Pre-cancer Dx: risk markers (BRCA); Dx (BCR-ABL); pre-Rx: prognostic (Ki67) or predict (guide Rx);… https://t.co/M0sTjeZa0d
De Bono #AACR19 Ex of markers: blood press; HIV viral load; HER2 and ER in Br cancer. Shows slide #3 from this FDA… https://t.co/jXPuc6QobX
De Bono #AACR19 Whole blood GEX (WBC), looking at myeloid cell's involvement with PrCa. Assuming: people knowing le… https://t.co/DjPhXf9SHh
De Bono #AACR19 PrCa: after Rx, 2-3 mo the drug doesn't work, you don't learn anything. Spent a lot of time w/CTC.… https://t.co/AM9qiz8cZD
De Bono #AACR19 Has been working on circulating biomarkers since '07; early trials 'were not really interpretable' - needed more info.
Johann De Bono (Royal Marsden UK) #AACR19 Impacting cancer research and patient care through circulating biomarkers