Deleterious alterations in homologous recombination repair genes and efficacy of platinum-based chemotherapy in biliary tract cancers.
Oncologist
; 29(8): 707-715, 2024 Aug 05.
Article
en En
| MEDLINE
| ID: mdl-38823036
ABSTRACT
BACKGROUND:
Platinum-based chemotherapy represents the standard first-line treatment for biliary tract cancers (BTC). Deficits in genes involved in the homologous recombination (HR) and DNA damage response (DDR) may confer higher sensitivity to platinum agents.METHODS:
We retrospectively included patients affected by BTC from 2 Italian institutions. Inclusion criteria consist of the receipt of platinum-based chemotherapy in the metastatic setting and the availability of comprehensive genomic profiling using next-generation sequencing (NGS). Patients were included in the HRD-like group if demonstrated oncogenic or likely oncogenic alterations in HR-/DDR-genes. Clinical endpoints were compared between the HRD-like group and the non-HRD-like group.RESULTS:
Seventy-four patients were included, of whom 25 (33%) in the HRD-like group and 49 (66%) in the non-HRD group. With a median follow-up of 26.04 months (interquartile-range [IQR] 9.41-29.27) in the HRD-like group and of 22.48 months (IQR 16.86-40.53) in the non-HRD group, no PFS difference emerged, with a mPFS of 5.18 months in the HRD-like group compared to 6.04 months in the non-HRD group (hazard ratio [HR], 1.017, 95% CI 0.58-1.78; Pâ =â .95). No differences were observed in DCR (64% [95 CI 45%-83%] vs 73% [95 CI 61%-86%]; Pâ =â .4), and CBR (45% [95% CI 28%-73%] vs 50% [95% CI, 37%-68%]; Pâ =â .9) between the HRD-like group and non-HRD groups, respectively. Median OS did not statistically differ between the HRD-like group and non-HRD group (26.7 vs 18.0 months, respectively; HR, 0.670, 0.33 to 1.37, Pâ =â .27).CONCLUSION:
HR-/DDR-genes, when assessed with regular tumor-only NGS panels, provide limited clinical validity to identify patients with BTC more likely to benefit from platinum-based chemotherapy.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias del Sistema Biliar
/
Reparación del ADN por Recombinación
Límite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Oncologist
/
Oncologist (Dayt. Ohio)
/
The oncologist (Dayton, Ohio. Online)
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia