Details

Autor(en) / Beteiligte

• Aung, Kyaw Lwin
• Fischer, Sandra
• Denroche, Rob
• Jang, Gun Ho
• Dodd, Anna
• Creighton, Sean
• Chadwick, Dianne
• Timms, Lee
• O'Kane, Grainne M.
• Albaba, Hamzeh
• Southwood, Bernadette M.
• Ghai, Sangeet
• Moore, Malcolm J.
• Miller, Jessica
• Notta, Faiyaz
• Wilson, Julie
• Hedley, David W.
• Dhani, Neesha C.
• Gallinger, Steven
• Knox, Jennifer J.

Titel

Prospective genomic/transcriptomic profiling of advanced pancreatic ductal adenocarcinoma (PDAC) for personalized therapy: Feasibility and preliminary results from the COMPASS study (NCT02750657)

Ist Teil von

• Journal of clinical oncology, 2017-05, Vol.35 (15_suppl), p.e15776-e15776

Erscheinungsjahr

2017

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Abstract only e15776 Background: Prospective characterization of advanced PDAC using whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) may identify patients (pts) who will benefit from a personalized treatment strategy. The feasibility of this approach has not previously been established in PDAC. Methods: Advanced PDAC pts with ECOG PS 0-1 and accessible metastatic or primary tumors, were recruited. A fresh tumor sample for WGS and WTS was obtained by percutaneous biopsy and a reference whole blood sample for germline DNA analysis collected before starting 1 st line palliative chemotherapy. Tumor biospecimens were enriched by laser capture microdissection before genomic analysis. The primary endpoint was feasibility (to report WGS results within 56 days in 40 of the first 50 recruited pts.) with a plan to accrue 200 pts. Results: From Dec 2015 – Jan 2017, 42 pts with advanced PDAC safely underwent tumor biopsy (32 liver, 1 omentum, 1 adrenal, 8 primary tumor). Adequate tumor biospecimens were obtained in all but one pt. The median number of tissue cores was 5 (range 3-6). The median post-enrichment tumor cellularity was 77% (range 37-93). WGS was successful for all samples analyzed. In 41 of 42 pts (97.6%), WGS was feasible and results were reported within 56 days (Median 37 days; range 19 to 52 days) meeting the primary endpoint. Potentially actionable somatic genetic aberrations were found in 12 pts (29%) involving ARID1A (N = 4), PIK3CA (N = 1), PDGFRB (N = 1), ERBB4 (N = 1), ATM (N = 2), CDK4 (N = 1) and CDK6 (N = 2). One pt with a germline BRCA2 mutation and another with somatic DSBR mutation signature achieved partial response with FOLFIRINOX (FFX). WTS results were available for 35 pts (85%). Of those, 19 were evaluable for FFX response. Eight of 9 pts (88%) with ‘classic’ signature and 4 of 10 pts (40%) with ‘basal like’ signature had tumor shrinkage with FFX (P = 0.08). Conclusions: Prospective comprehensive genomic profiling of advanced PDAC is feasible with an acceptable turnaround time. Approximately 30% of advanced PDAC pts have targetable genomic signatures and aberrations. RNA signature may predict FFX response.