Cancer Treatment Today

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. A recent phase 2 Study by Gerard-Otero et al found that the combination of ribociclib and letrozole is associated with a promising 50% and 55% PFS12 in patients with ER-positive relapsed OC or EC respectively.

This therapy is still being studied and it is E/I and not medically necessary. It is in clinical trial: Palbociclib Plus Letrozole Treatment After Progression to Second Line Chemotherapy for Women With ER/PR-positive Ovarian Cancer. (LACOG1018), ClinicalTrials.gov Identifier: NCT03936270

Iyengar M, O’Hayer P, Cole A, et al. CDK4/6 inhibition as maintenance and combination therapy for high grade serous ovarian cancer. Oncotarget. 2018;9(21):1565815672. Published 2018 Feb 26. doi:10.18632/oncotarget.24585

Gerardo Colon-Otero, S. John Weroha, Va et al, Results of a phase 2 trial of ribociclib and letrozole in patients with either relapsed estrogen receptor (ER)-positive ovarian cancers or relapsed ER-positive endometrial cancers. ournal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 5510-5510.

Daniele Frisone, Melinda Charrier, Sophie Clement, Yann Christinat, Laure Thouvenin, Krisztian Homicsko, Olivier Michielin, Alexandre Bodmer, Pierre O. Chappuis, Thomas A. McKee & Petros Tsantoulis (2020) Durable response to palbociclib and letrozole in ovarian cancer with CDKN2A loss, Cancer Biology & Therapy, 21:3, 197-202,