Genomic Methods Identify Homologous Recombination Deficiency in Pancreas Adenocarcinoma and Optimize Treatment Selection.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
03
02
2020
revised:
07
03
2020
accepted:
08
04
2020
pubmed:
24
5
2020
medline:
15
9
2021
entrez:
24
5
2020
Statut:
ppublish
Résumé
Genomic methods can identify homologous recombination deficiency (HRD). Rigorous evaluation of their outcome association to DNA damage response-targeted therapies like platinum in pancreatic ductal adenocarcinoma (PDAC) is essential in maximizing therapeutic outcome. We evaluated progression-free survival (PFS) and overall survival (OS) of patients with advanced-stage PDAC, who had both germline- and somatic-targeted gene sequencing. Homologous recombination gene mutations (HRm) were evaluated: Among 262 patients, 50 (19%) had HRD (15% germline and 4% somatic). Both groups were analyzed together due to lack of difference in their genomic instability and outcome. Median [95% confidence interval (CI)] follow-up was 21.9 (1.4-57.0) months. Median OS and PFS were 15.5 (14.6-19) and 7 (6.1-8.1) months, respectively. Patients with HRD had improved PFS compared with no HRD when treated with first-line (1L) platinum [HR, 0.44 (95% CI: 0.29-0.67); Pathogenic HRm identifies HRD in patients with PDAC with the best outcome when treated with 1L-platinum. Biallelic HRm and core HRm further enriched benefit from 1L-platinum from HRD.
Identifiants
pubmed: 32444418
pii: 1078-0432.CCR-20-0418
doi: 10.1158/1078-0432.CCR-20-0418
pmc: PMC7380542
mid: NIHMS1585312
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3239-3247Subventions
Organisme : NCI NIH HHS
ID : K08 CA248964
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA184746
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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