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

Authors
  • Frisone, Daniele1
  • Charrier, Melinda1
  • Clement, Sophie2
  • Christinat, Yann2
  • Thouvenin, Laure1
  • Homicsko, Krisztian3
  • Michielin, Olivier3
  • Bodmer, Alexandre1
  • Chappuis, Pierre O.1, 2
  • McKee, Thomas A.2
  • Tsantoulis, Petros1, 4
  • 1 Department of Oncology, University Hospitals of Geneva (HUG), Switzerland , (Switzerland)
  • 2 Department of Genetic Medicine, Laboratory and Pathology, University Hospitals of Geneva (HUG), Switzerland , (Switzerland)
  • 3 Multidisciplinary Oncology Center, Lausanne University Hospital (CHUV), Switzerland , (Switzerland)
  • 4 Department of Medical Specialties Faculty of Medicine, University of Geneva, Switzerland , (Switzerland)
Type
Published Article
Journal
Cancer Biology & Therapy
Publisher
Landes Bioscience
Publication Date
Nov 10, 2019
Volume
21
Issue
3
Pages
197–202
Identifiers
DOI: 10.1080/15384047.2019.1685291
PMID: 31709901
PMCID: PMC7012162
Source
PubMed Central
Keywords
License
Green

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.

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