Durable response to palbociclib and letrozole in ovarian cancer with CDKN2A loss.

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_DDF548EFECDC
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Durable response to palbociclib and letrozole in ovarian cancer with CDKN2A loss.
Journal
Cancer biology & therapy
Author(s)
Frisone D., Charrier M., Clement S., Christinat Y., Thouvenin L., Homicsko K., Michielin O., Bodmer A., Chappuis P.O., McKee T.A., Tsantoulis P.
ISSN
1555-8576 (Electronic)
ISSN-L
1538-4047
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
21
Number
3
Pages
197-202
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Alterations of the Retinoblastoma (Rb) pathway are frequent in ovarian cancer, typically resulting from CDKN2A down-regulation, CCNE1 amplification, CCND1/2 amplification, and RB1 loss. However, bi-allelic CDKN2A mutation or homozygous deletion is a very rare event, concerning less than 5% of patients.Initial trials with palbociclib in serous ovarian cancer have shown very modest benefit in unselected patient populations, thus underlining the need for a biomarker predicting response. We report the case of a heavily pre-treated patient with a serous ovarian tumor harboring a homozygous deletion of the CDKN2A gene that derived significant, prolonged clinical benefit from palbociclib, a CDK4/6 oral inhibitor, with letrozole. Treatment with palbociclib and letrozole started on February 2018, with an ongoing response after 12 months.In conclusion, homozygous CDKN2A deletion is rare and could be used to predict response to CDK4/6 inhibitors in association with other genomic features. We encourage further trials in this direction.
Keywords
Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Biomarkers, Tumor/genetics, Cyclin E/genetics, Cyclin-Dependent Kinase Inhibitor p16/genetics, Cystadenocarcinoma, Serous/drug therapy, Cystadenocarcinoma, Serous/genetics, Cystadenocarcinoma, Serous/pathology, Female, Gene Amplification, Humans, Letrozole/administration & dosage, Middle Aged, Neoplasm Recurrence, Local/drug therapy, Neoplasm Recurrence, Local/genetics, Neoplasm Recurrence, Local/pathology, Oncogene Proteins/genetics, Ovarian Neoplasms/drug therapy, Ovarian Neoplasms/genetics, Ovarian Neoplasms/pathology, Piperazines/administration & dosage, Prognosis, Pyridines/administration & dosage, Retinoblastoma Binding Proteins/genetics, Sequence Deletion, Ubiquitin-Protein Ligases/genetics, CDK4/6 inhibitors, CDKN2A loss, Ovarian cancer, palbociblib, precision oncology
Pubmed
Web of science
Open Access
Yes
Create date
14/11/2019 9:20
Last modification date
21/11/2022 8:28
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