Tzou: Study issues include discordance between orthogonal methods; tissue with and without outcome data #FDA_AACR
1:52pm July 19th 2016 via Hootsuite
Tzou: Also concordance between tissue and plasma; need to connect device results w/clinical outcome #FDA_AACR
1:48pm July 19th 2016 via Hootsuite
Tzou: Issue of diff's in analytical status, and 'contrived samples' and their equivalence. Representation of pt population needed #FDA_AACR
1:47pm July 19th 2016 via Hootsuite
Abraham Tzou (FDA) CDRH considerations for liquid biopsy diagnostic development #FDA_AACR
1:44pm July 19th 2016 via Hootsuite
Q: Sample size stats? A:Decided on presubmission, for intended use. Q:Open to negotiation? A: Yes. #FDA_AACR
1:41pm July 19th 2016 via Hootsuite
Case study w/cobas EGFR: Used dPCR for a qPCR assay; NGS more deeply. Many times 'found tissue was wrong, ctDNA showed orthogonal' #FDA_AACR
1:35pm July 19th 2016 via Hootsuite
Q: CNV from ctDNA? Discussion around whether or not CNV detection is accurate; clinical validation; clinical utility as well. #FDA_AACR
11:44am July 19th 2016 via Hootsuite
Discussion at the #FDA_AACR about existing tests and lack of consistency between test providers. Oxnard "let them be graded"
11:42am July 19th 2016 via Hootsuite
A2: Oxnard: He will use and do 'whatever I can do' for the benefit of the pt. and use whatever is available #FDA_AACR
11:25am July 19th 2016 via Hootsuite
Q: What is a 'tissue biopsy'? Core needles? Resection? Sequist: Dictated by confines of the trial. FNAs, block better than cores #FDA_AACR
11:23am July 19th 2016 via Hootsuite
RT @Liquid_Biopsy_: Liquid Biopsy early screening for lung cancer https://t.co/6EXfeGjOcF
11:19am July 19th 2016 via Twitter Web Client
RT @AACR: Today’s #FDA-AACR workshop on “Liquid Biopsies in Oncology Drug and Device Development” is underway. https://t.co/fkE6qoKsmV
11:16am July 19th 2016 via Hootsuite
Thress: Complexity where NGS reveals trans mutations '16 Nature https://t.co/7ayqN8ENWg #FDA-AACR
11:11am July 19th 2016 via Hootsuite
Thress: '16 ref https://t.co/LKfMN4b6DA Allelic context for C797S also may matter, 1 example published T790M in trans #FDA-AACR
11:10am July 19th 2016 via Hootsuite
Kenneth Thress (AstraZeneca) Using NGS w/3rd-gen TKIs; C797S-mediated acquired resistance. '15 ref https://t.co/tLtZCRxcLJ #FDA-AACR
11:07am July 19th 2016 via Hootsuite
David Shames (Genentech) B-FAST study, new clinical study w/pts with EGFR, ALK and RET mutations using Foundation Med #FDA-AACR
11:04am July 19th 2016 via Hootsuite
Sequist: Ongoing work with iChip, reviews method '13 ref https://t.co/DkeGiOAhdv #FDA-AACR
11:00am July 19th 2016 via Hootsuite
Sequist: Thus great interest in CDx to improve specificity for NSCLC early screen. '14 PLOS https://t.co/3vXgM47g3q CTC early det #FDA-AACR
10:53am July 19th 2016 via Hootsuite
Sequist: '11 NEJM https://t.co/7F4VlBWnVd low-dose CT scans rec'd; but of 24% who had notdule, 96% FPs (!) $1.2B/y #FDA-AACR
10:51am July 19th 2016 via Hootsuite
Sequist: New topic: screening for early-stage lung ca. 226K cases, 158k deaths yearly. NLST - 55-75y, no signs or symptoms #FDA-AACR
10:50am July 19th 2016 via Hootsuite
Sequist: 'Tests are multiplying like rabbits'; need to be cautious until we have data that it improves outcome #FDA-AACR
10:49am July 19th 2016 via Hootsuite
Sequist: "Risk stratification not necessarily helpful unless you can act to modify the risk." #FDA-AACR
10:48am July 19th 2016 via Hootsuite
Sequist: SWOG SO500 study - >5 CTCs (CellSearch), n=288, treatment naive. '14 ref https://t.co/aYjd1jvSuK OS and PFS no effect #FDA-AACR
10:47am July 19th 2016 via Hootsuite
Sequist: Uses cobas EGFR PCR ctDNA test; FAST-ACT2 trial, chemo w/erlotinib or placebo. '15 ref https://t.co/Ncse6ODg4Q #FDA-AACR
10:44am July 19th 2016 via Hootsuite
Sequist: Serial ctDNA can corr. w/outcome. Plasma and radiographs. Larger study '15 https://t.co/U1iRR5uRQv fast/slow responders #FDA-AACR
10:42am July 19th 2016 via Hootsuite
Sequist: Traditionally, new Rx started and wait 8w to determine response via CT scan. Shows data '15 https://t.co/X5N9N9w6Ti #FDA-AACR
10:40am July 19th 2016 via Hootsuite
Lecia Sequist (Mass Gen Hosp MA) Liquid biopsies for trtmt monitoring, risk stratification, and early detection #FDA-AACR
10:38am July 19th 2016 via Hootsuite
Oxnard: Pt3 - is this recurring NSCLC? Data for ctDNA is unclear. Tumor NGS can change Dx, from pre-existing Dx #FDA-AACR
10:29am July 19th 2016 via Hootsuite
Oxnard: Pt3: 74yo M never-smoker, prior hist of resected NSCLC. Bone biopsy challenging. ctDNA EGFR L858R, 3.5% #FDA-AACR
10:28am July 19th 2016 via Hootsuite
Oxnard: Boehringer starting ELUXA6 PhII study - going straight to ctDNA test #FDA-AACR
Oxnard: 6w - too ill for tissue biopsy. L858 found at 2%. Started off-label osimertinib. 'Unclear 'ref std' for resistance muts' #FDA-AACR
10:27am July 19th 2016 via Hootsuite
Oxnard: Based on this data - T790M assay first, if 790M+ skip biopsy, start 3rd-gen TKI. Pt2 - continue erlotinib, visit in 2mo #FDA-AACR
10:25am July 19th 2016 via Hootsuite
Oxnard: Used PI AURA trial, sent to BEAMing (Sysmex-Inostics) w/AstraZeneca. '16 JCO https://t.co/D6g3B6jZBQ T790M neg do better #FDA-AACR
10:24am July 19th 2016 via Hootsuite
Oxnard: Difficult to access lesion for biopsy. cfDNA shows L878R 'detected at <1% AF'; T790M not detected #FDA-AACR
10:22am July 19th 2016 via Hootsuite
Oxnard: Pt2 73yo F w/EGFR-mut NSCLC, presents on erlotinib at 2y. Now Osimertinib, 62% resp rate, 9.7 PFS #FDA-AACR
Oxnard: Sens. of ~80% for ctDNA, so negatives can't be trusted. Now DFCI starting NCT02770014 using ddPCR #FDA-AACR
10:20am July 19th 2016 via Hootsuite
Oxnard: Pt1: erlotinib initiated, pt symptoms rapidly improve. There are practical / logistical challenges for tumor genotyping #FDA-AACR
10:19am July 19th 2016 via Hootsuite
Oxnard: 1 met site ~60%, goes up to 80% w/4 met sites. Zero FP rate; 63% spec for T790M resistance mut #FDA-AACR
10:18am July 19th 2016 via Hootsuite
Oxnard: 3d vs 27d - '16 JAMA Onc https://t.co/Yfwn1KbUyi Oveal sens 64%-82% detection increases w/increased burden #FDA-AACR
10:17am July 19th 2016 via Hootsuite
Oxnard: Reviews EGFR genotyping in tumor - 8 days for test, but clinical course takes longer still. For liquid biopsy: fast #FDA-AACR
10:16am July 19th 2016 via Hootsuite
Oxnard: Brain MRI shows cerebellar lesion, supraclav biopsy shows NSCLC. #FDA-AACR
10:15am July 19th 2016 via Hootsuite
Oxnard: Newly Dx NSCLC, acquired TKI resistance, 3rd example will be presented. First - 49yo M never-smoker #FDA-AACR
10:14am July 19th 2016 via Hootsuite
Geoffrey Oxnard (Dana-Farber / Harvard) Plasma genotyping for treatment selection in advance NSCLC #FDA-AACR
10:13am July 19th 2016 via Hootsuite
Tewari: A non-linear, complex model of disease progression hit the 'window of opportunity' where intervention can occur #FDA-AACR
9:41am July 19th 2016 via Hootsuite
Tewari: Refers to '97 systems biology book https://t.co/YsfyhAv28p and how day-to-day, and person-to-person variation impacts #FDA-AACR
9:40am July 19th 2016 via Hootsuite
Tewari: Thus confusion w/conflicting results. NIH and others are working on standardizing methods. https://t.co/S1O5pUAFCO #FDA-AACR
9:36am July 19th 2016 via Hootsuite
Tewari: Onto exosomes, one of multiple classes of EVs; all purification methods co-purify ribonucleoprotein complexes #FDA-AACR
9:34am July 19th 2016 via Hootsuite
Tewari: 98% is protected by Ago2; 2% assoc'd with exosomes. Continuing to expand - 3K papers, including forensics #FDA-AACR
9:29am July 19th 2016 via Hootsuite
Tewari: exDNA is highly specific, less dynamic, 1 or 2 copies/cel; exRNA more dynamic, can inform cell type/state #FDA-AACR
9:28am July 19th 2016 via Hootsuite
Tewari: '08 PNAS https://t.co/gT02BgBBVb showed stability; miR-200a/c that were EMT-spec. miR-210, poss. marker for hypoxia #FDA-AACR
9:25am July 19th 2016 via Hootsuite
