Highlights
- •The role of altered DNA damage repair pathways in BTC setting is already unknown.
- •We conducted a retrospective analysis on BTC patients treated with platinum salts.
- •BRCAness phenotype is an independent favourable prognostic factor for PFS.
- •BRCAness BTC patients seem to be more sensitive to platinum compounds.
- •Sequential strategies of platinum salts and PARP inhibitors should be tested.
Abstract
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.
Keywords
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Article info
Publication history
Published online: June 21, 2022
Accepted:
May 2,
2022
Received in revised form:
April 22,
2022
Received:
October 29,
2021
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
