In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 273-273
Abstract:
273 Background: Substantial progress has been made in the understanding of the genomic landscape of PDAC, but the clinical utility of these data remains uncertain. Methods: As part of the BC Cancer Personalized Oncogenomics (POG) and PanGen studies, whole genome analysis and transcriptome sequencing were performed on fresh biopsy and blood sample from 47 mPDAC patients. Genomic findings informed therapy choices including potential eligibility for the CCTG PM.1 molecular basket trial. Results: Cohort consists of 53% male, average age 57.8, 34/47 had ≥2 lines of treatment. 37/47 biopsies were from liver and 26/47 were collected pre-treatment. 8/47 (17%) patients had aberrations with strong evidence of clinical actionability. These include 2 germline BRCA2, 1 germline BRCA1, 1 somatic XRCC2 homozygous deletion with strong COSMIC signature 3, all predictive of platinum sensitivity. Patients with XRCC2 deletion and BRCA1 had over 2 years on FOLFIRINOX. Fusions affecting the NRG1 gene were identified in 3 patients, all with KRAS wildtype tumours, which may confer ERRB inhibitor sensitivity. 1/3 NRG1 fusion patients had thus far been treated with the ERBB inhibitor afatinib, with reduction of CA19-9 from 〉 120,000 to 7246 and dramatic response noted on PET CT imaging one month post treatment. One patient had mismatch repair deficiency, and a high mutational burden, suggestive of immune checkpoint inhibitor sensitivity. In total 85% (40/47) sequenced mPDAC patients had potentially actionable mutations which includes CCTG PM.1 trial eligibility: 24/47 with cell cycle dysregulation (CDK4/6 inhibitor arm), 4/47 with high homologous recombination defects (PARP inhibitor arm), 1/47 ERBB2 amplification (anti-HER2 arm), 2/47 high expression of FGFR1 (Sunitinib arm) and 1/47 with high FLT4 and IGF1R expression (Axitinib arm). Conclusions: More routine use of comprehensive genomic analysis should be considered in mPDAC given finding of high degree of actionability. Importantly, a significant proportion (17%) had findings with strong evidence of clinical impact.(NCT02155621, NCT02869802, NCT03297606)
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.4_suppl.273
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
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