Kefah Mokbel: Rethinking Progression on CDK4/6 Inhibitors in Breast Cancer

Kefah Mokbel, Chair of Breast Cancer Surgery at London Breast Institute and Honorary Professor of Medicine at Cardiff University School of Medicine, shared a post on LinkedIn:

“Rethinking Progression on CDK4/6 Inhibitors: Distinct Phenotypes, Distinct Outcomes

Recent data published in Clinical Breast Cancer provide important insights into progression patterns in patients treated with CDK4/6 inhibitors:

1.  Approximately two-thirds of patients developed polyprogressive disease, with 90% experiencing repeat polyprogression.
2.  Among those with oligoprogressive disease, two-thirds had repeat oligoprogression, while the remainder transitioned to induced oligoprogression (IO).
3. Four distinct clinical phenotypes demonstrated significant differences in progression-free and overall survival, highlighting the biological and clinical heterogeneity of disease evolution.
4. Notably, continuation of CDK4/6 inhibitors beyond progression did not adversely impact survival in patients with oligoprogressive disease – particularly those with IO – supporting a more nuanced, individualized treatment approach.
5. Clinical factors associated with progression patterns included:

•  BMI ≥ 25 kg/m² – higher likelihood of oligoprogression
•  High-grade tumors, HER2-low disease, and early progression (<6 months) – higher likelihood of polyprogression

These findings reinforce the importance of phenotype-driven management strategies in advanced breast cancer and the need for prospective validation with molecular correlates.

In our institutional practice, we do not routinely discontinue CDK4/6 inhibitors in the setting of isolated progression.

Instead, we adopt a biologically driven approach:
The progressing clone is managed with local ablative strategies, such as stereotactic ablative radiotherapy (SABR) or surgery, while systemic therapy is continued.

This strategy reflects the concept of oligoprogression, where resistant subclones can be eradicated locally, potentially prolonging the benefit of ongoing targeted therapy.”

Title: Patterns of Disease Progression in Advanced Breast Cancer Patients Treated With Cyclin D Kinase 4/6 Inhibitors: Prognostic and Therapeutic Implications

Authors: Sudhir Kumar, Neha Pathak, Rossanna C. Pezo

Read The Full Article.

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