Gene mutational profile of BRCAness and clinical implication in predicting response to platinum-based chemotherapy in patients with intrahepatic cholangiocarcinoma.
BRCAness phenotype
Biliary tract cancer
PARP inhibitors
Platinum-based chemotherapy
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
29
10
2021
revised:
22
04
2022
accepted:
02
05
2022
pubmed:
25
6
2022
medline:
20
7
2022
entrez:
24
6
2022
Statut:
ppublish
Résumé
Biliary tract cancers are rare malignancies with a poor prognosis and scarce therapeutic strategies. The significance of BRCAness in this setting is already unknown. Tissue specimens of BTC patients treated with platinum-based chemotherapy have been analyzed through the FOUNDATIONPne assay. 72/150 (48%) BRCAness mutated and 78/150 (52.0%) wild type (WT) patients were included. The most commonly mutated genes in the BRCAness mutated group were: ARID1A (N = 32, 44%), CDKN2A (N = 23, 32%), KRAS/NRAS (N = 16, 22%), CDKN2B (N = 13, 18%), BRCA2 (N = 13, 18%), PBRM1 (N = 12, 17%), ATM (N = 11, 15%), FGFR2 (N = 10, 14%), TP53 (N = 8, 11%), IRS2 (N = 7, 10%), CREBBP (N = 7, 10%) (table 3, figure 1). At the univariate analysis BRCAness mutation was associated with longer median Progression Free Survival (mPFS) (HR 0.68; 95% CI 0.49-0.95; p = 0.0254); it was not associated with longer mOS but a trend toward a benefit in survival was found (HR 0.77; 95% CI 0.50-1.19; p = 0.2388). Patients with BRCAness mutation showed a higher percentage of disease control rate (77.8 vs 67.9; p = 0.04) compared to patients WT. Multivariate analysis confirmed BRCAness mutation (HR 0.66; 95% CI: 0.45-0.98; p = 0.0422) as independent favorable prognostic factors for PFS and a positive trend was found for OS (HR 0.84; 95% CI: 0.53-1.33; p = 0.3652). BRCAness BTC patients showed a better PFS compared BRCAnessWT patients after exposure to platinum-based chemotherapy. Moreover, the OS curves' trend showed in our analysis suggests that BRCAness mutated patients could benefit from a maintenance therapy with PARPi.
Sections du résumé
BACKGROUND AND AIMS
Biliary tract cancers are rare malignancies with a poor prognosis and scarce therapeutic strategies. The significance of BRCAness in this setting is already unknown.
METHOD
Tissue specimens of BTC patients treated with platinum-based chemotherapy have been analyzed through the FOUNDATIONPne assay.
RESULTS
72/150 (48%) BRCAness mutated and 78/150 (52.0%) wild type (WT) patients were included. The most commonly mutated genes in the BRCAness mutated group were: ARID1A (N = 32, 44%), CDKN2A (N = 23, 32%), KRAS/NRAS (N = 16, 22%), CDKN2B (N = 13, 18%), BRCA2 (N = 13, 18%), PBRM1 (N = 12, 17%), ATM (N = 11, 15%), FGFR2 (N = 10, 14%), TP53 (N = 8, 11%), IRS2 (N = 7, 10%), CREBBP (N = 7, 10%) (table 3, figure 1). At the univariate analysis BRCAness mutation was associated with longer median Progression Free Survival (mPFS) (HR 0.68; 95% CI 0.49-0.95; p = 0.0254); it was not associated with longer mOS but a trend toward a benefit in survival was found (HR 0.77; 95% CI 0.50-1.19; p = 0.2388). Patients with BRCAness mutation showed a higher percentage of disease control rate (77.8 vs 67.9; p = 0.04) compared to patients WT. Multivariate analysis confirmed BRCAness mutation (HR 0.66; 95% CI: 0.45-0.98; p = 0.0422) as independent favorable prognostic factors for PFS and a positive trend was found for OS (HR 0.84; 95% CI: 0.53-1.33; p = 0.3652).
CONCLUSION
BRCAness BTC patients showed a better PFS compared BRCAnessWT patients after exposure to platinum-based chemotherapy. Moreover, the OS curves' trend showed in our analysis suggests that BRCAness mutated patients could benefit from a maintenance therapy with PARPi.
Identifiants
pubmed: 35749808
pii: S0959-8049(22)00282-9
doi: 10.1016/j.ejca.2022.05.004
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Organoplatinum Compounds
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
232-241Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DR. TERESA MACARULLA MERCADE. Dr. Teresa Macarulla reports honoraria for consultancy from (SOBI) Swedish Orpahn Biovitrum AB, Ability Pharmaceuticals SL, Advance Medical HCMS, S.A., Aptitude Health, AstraZeneca, Basilea Pharma, Baxter, BioLineRX Ltd, Celgene, Eisai, Genzyme, Got It Consulting SL, IATTGI, Imedex, Incyte, Ipsen Bioscience, Inc, Laboratorios Menarini, Lilly. Marketing Farmacéutico & Investigación Clínica, S.L, MDS, Medscape, Monte Verde SA, Novocure, Paraxel, PPD Development, QED Therapeutics, Roche Farma, Sanofi-Aventis, Servier, TRANSWORLD EDITORS, SL and Zymeworks. Dr. Teresa Macarulla declares institutional interest in form of financial support for clinical trials or contracted research: Agios, Aslan, AstraZecena, Bayer, Celgene, Genentech, Hallozyme, Immunomedics, Lilly, Merimarck, Millenim, Novartis, Pfizer, Pharmacyclics, and Roche. DR. HELENA VERDAGUER MATA declares: speaker's Bureau: Astrazeneca. Advisory Role: Merck. OTHER COAUTHORS: Declare no conflict of interest.