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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• The Retinoblastoma (Rb) pathway is frequently altered in ovarian cancer, involving genes like CDKN2A, CCNE1, CCND1/2, and RB1.
• Bi-allelic CDKN2A mutation or homozygous deletion is uncommon, affecting less than 5% of ovarian cancer patients.
• Previous trials of palbociclib in serous ovarian cancer showed limited benefit in unselected populations, highlighting the need for predictive biomarkers.

Observation:

• A heavily pre-treated patient with serous ovarian cancer presented with a homozygous deletion of the CDKN2A gene.
• This patient received palbociclib, a CDK4/6 inhibitor, in combination with letrozole.
• Treatment commenced in February 2018, and the patient experienced a significant and ongoing clinical response for over 12 months.

Findings:

• The patient with homozygous CDKN2A deletion demonstrated a significant and prolonged clinical benefit from palbociclib and letrozole therapy.
• This case suggests that homozygous CDKN2A deletion is a potential predictive biomarker for response to CDK4/6 inhibitors.

Implications:

• Homozygous CDKN2A deletion, though rare, may serve as a biomarker to identify ovarian cancer patients likely to benefit from CDK4/6 inhibitors.
• Combining genomic information, such as CDKN2A deletion status, with other features could refine patient selection for targeted therapies.
• Further clinical trials are warranted to validate homozygous CDKN2A deletion as a predictive biomarker for CDK4/6 inhibitor therapy in ovarian cancer.