Raponi: Foundation Medicine partner w/Clovis - not only BRCA1/2, also SNVs and LOH. Reviews FOne assay, showed optimal LOH cutoff #NGDx16
12:10pm August 23rd 2016 via Hootsuite
Raponi: HRD causes genome-wide LOH, using SNP assays. Two samples were BRCAwt; LOH phenotype clearly shown in one. #NGDx16
12:07pm August 23rd 2016 via Hootsuite
Raponi: Non-BRCA HR-pathway gene mutations are rare (cumulative freq = 13%) while looking at large regions of LOH or CNV #NGDx16
12:06pm August 23rd 2016 via Hootsuite
Raponi: BRCA may have 100's of mutations, fn relevance of BRCA1 methylation status 'questionable' #NGDx16
12:05pm August 23rd 2016 via Hootsuite
Raponi: To predict response, all genes not created equal; four w/strong siRNA knockdown effect (RAD51, BRCA1/2); others less sens #NGDx16
12:04pm August 23rd 2016 via Hootsuite
Raponi: Up to 50% HGOC (high-grade serous ovarian ca) pts may be tBRCAmut or BRCA-like per TCGA. #NGDx16
12:02pm August 23rd 2016 via Hootsuite
Raponi: Synthetic lethality: if a cell competent in homol. repair; cell can survive. With PARPi, cell deficient in HR = cell death #NGDx16
12:00pm August 23rd 2016 via Hootsuite
Raponi: Clovis awarded breakthrough designation for their PARPi; several ongoing PhII/PhIII studies in ovarian cancer #NGDx16
11:59am August 23rd 2016 via Hootsuite
Mitch Raponi (Clovis Oncology): NGS-based companion Dx for ID of ovarian cancer pts likely to respond to Rucaparib (PARP inh) #NGDx16
11:57am August 23rd 2016 via Hootsuite
Q: ALK/RET/ROS detection? Scudder: Study may come out from AstraZeneca #NGDx16
11:56am August 23rd 2016 via Hootsuite
Q: Obs differences between plasma and serum? Scudder: In this study we did not, in one study where serum was collected instead #NGDx16
11:55am August 23rd 2016 via Hootsuite
Q: Tech variability vs biological? Scudder: Sequential testing gives insight into biological var. #NGDx16
11:53am August 23rd 2016 via Hootsuite
Q: Rough costs of approval ex-clin studies? Scudder: "Well over $10M" #NGDx16
11:51am August 23rd 2016 via Hootsuite
Q: May it become easier to approve in future? Scudder: FDA was very collaborative; as they become more comfortable -> may be easier #NGD
Scudder: Concl3: they being the first may be considered a benchmark for further tests to become approved. #NGDx16
11:50am August 23rd 2016 via Hootsuite
Scudder: Concl 2: ctDNA is viable alternative; further clin studies needed for non-invasive testing to become routine #NGDx16
11:49am August 23rd 2016 via Hootsuite
Scudder: Tissue tests are still gold std; but clin utility of plasma testing mirrors utility of tissue testing #NGDx16
Scudder: Potential for ctDNA - response, monitoring. open Q: molecular progression vs. clinical progression post-Rx? #NGDx16
11:48am August 23rd 2016 via Hootsuite
Scudder: Same utility for erlotinib bet plasma and tissue. 0.29 hazard ratio. Sens analysis: shows PPV going up with EGFR prevalence #NGDx16
11:47am August 23rd 2016 via Hootsuite
Scudder: Clinical validity, PPA 76%; NPA 98%; overall 87%. Clin utility ENSURE tiral, PhII, shows K-M curve of plasma to tissue #NGDx16
11:46am August 23rd 2016 via Hootsuite
Scudder: invalid rate 0.33% (4/1224 tests). #NGDx16
11:44am August 23rd 2016 via Hootsuite
Scudder: 3 sites, 3 lots, 2 panels. Showed only 1 missed at 1x LoD from all these studies. Clin reprod: 3 lots, 3 sites, 2 operator #NGDx16
11:43am August 23rd 2016 via Hootsuite
Scudder: 3 muts - Exon 19del, L858R, T790M. 8 levels 0.03x - 10x LoD, 20 replicates/panel. #NGDx16
11:42am August 23rd 2016 via Hootsuite
Scudder: 72 replicates across 3 lots; wtDNA of approx 100K copies/mL. LoD was down to 25 to 100 copies/mL. LoD was set 100 copies #NGDx16
Scudder: Contrived sample performance - determined LoD w/sheared cell-line DNA. 8L of NSCLC plasma? 'we managed to do that' #NGDx16
11:41am August 23rd 2016 via Hootsuite
Scudder: ddPCR not easily multiplexed; FDA rec'd non-PCR approach; cobas assay is 'at least 42 mutations' #NGDx16
11:40am August 23rd 2016 via Hootsuite
Scudder: Approval - no stds, ref methods; needed to validate sens/spec; det methods may be affected by normal background #NGDx16
11:39am August 23rd 2016 via Hootsuite
Scudder: Rapid and slow responders - longitudinal data showing clearance, NGDx16
11:38am August 23rd 2016 via Hootsuite
Scudder: Aarhus - https://t.co/8dfEaatYgK also data from Thress at ASCO https://t.co/zU38eArnFO EGFR allele-spec PCR vs NGS equiv. #NGDx16
11:37am August 23rd 2016 via Hootsuite
Scudder: Fastact-2 results reviewed OS and PFS '13 ref https://t.co/bwk2P97v80 plasma collected https://t.co/dMQK41hUfE #NGDx16
11:33am August 23rd 2016 via Hootsuite
Scudder: Shows summary of FASTACT-2, Arhus, Clovis CO-1686 studies. FASTACT-2 had 88% overall agreement. 75% sens 96% spec #NGDx16
11:31am August 23rd 2016 via Hootsuite
Scudder: Specimen acquisition a challenge, reference methods 'how is truth established between tissue and plasma' #NGDx16
11:30am August 23rd 2016 via Hootsuite
Scudder: Lays out limitations of tissue; customer (physician, pt) needs fast TAT, accurate, cost-effective. FDA collab needed #NGDx16
11:29am August 23rd 2016 via Hootsuite
Scudder: Multiple other mutations are there; EGFR is not performed for ~20% of eligable NSCLC pts, from 562 oncologists worldwide #NGDx16
Scudder: 1st liquid biopsy test approved, June '16. L861Q in v2; intended use is 'long and complex'. Co-Dx for tarceva, tagrisso #NGDx16
11:28am August 23rd 2016 via Hootsuite
Sid Scudder (Roche): Clinical utility of the cobas EGFR mutation test v2 from liquid biopsy samples in pts with NSCLC #NGDx16
11:27am August 23rd 2016 via Hootsuite
RT @h2so4hurts: AS: Going over cases where the "pathogenic" gene doesn't correlate with the literature - found HGMD/OMIM lagging well behin…
11:23am August 23rd 2016 via Twitter Web Client
Mazumder: IHC bridging study: PPA 93.1%, neg % agreement 71%. Ultimately - impact on testing population #NGDx16
11:23am August 23rd 2016 via Hootsuite
Mazumder: Low risk (CTA to IUO); then mutation via seq to qPCR; highest is switch from tissue to plasma, or from dPCR to other PCR #NGDx16
11:22am August 23rd 2016 via Hootsuite
Mazumder: Bridging studies: higher regulatory risk. Refers to Donna Roscoe's FDA presentation; 90% retest population rep of use pop. #NGDx16
11:21am August 23rd 2016 via Hootsuite
Mazumder: What does the label look like? Cobas: "reflex to the tissue" so you have to think through the logistics of this #NGDx16
11:20am August 23rd 2016 via Hootsuite
Mazumder: T790M in multiple biopsies, '15 ref https://t.co/vJoPQOuY8a CTC vs all biopsy = 74%; ctDNA vs all biopsy 61% #NGDx16
11:19am August 23rd 2016 via Hootsuite
Mazumder: '15 Joosse review: https://t.co/bLlO7Uky7m Daber and Velculescu rev https://t.co/ocGDsN2iH0 complementary info CTC ctDNA #NGDx16
11:17am August 23rd 2016 via Hootsuite
Mazumder: Pos Pred Agreement between platforms was 78-89%. #NGDx16
11:14am August 23rd 2016 via Hootsuite
Mazumder: '03 ref https://t.co/Si1Ps7HLn9 IHC vs 3 gene expression platforms; showed data from AACR '16, overall concordance 80% #NGDx16
11:13am August 23rd 2016 via Hootsuite
Mazumder: Shows data on Ki67 reprod; '13 ref https://t.co/QJplRkT6hi what can be inferred about PDL-1 assays? #NGDx16
11:12am August 23rd 2016 via Hootsuite
Mazumder (Janssen Dx) Shows data from DLBCL ibrutinib '15 ref https://t.co/mgmdxReI6N IHC vs NGS; went with IHC #NGDx16
11:09am August 23rd 2016 via Hootsuite
Raponi: Example therascreen for T790M EGFR, couldn't get the label. Another with germline BRCA '15 ref https://t.co/XkS1M4z9yp #NGDx16
11:06am August 23rd 2016 via Hootsuite
Raponi: Analytical/clin validation for rare mutations may be challenging - what about 1% prevalence? BRCA? Can impact Dx, Rx label #NGDx16
11:05am August 23rd 2016 via Hootsuite
Companion Dx session at #NGDx16 (Raponi, Clovis) Intro comments - pre-screening may lead to bias; reprod around the cut-off crucial
11:04am August 23rd 2016 via Hootsuite
