Subsequent Treatments After Progression on Cyclin-Dependent Kinase 4/6 Inhibitors: A Review of the Evidence and a Real-World Data Perspective From Portuguese Hospitals.

Authors

Rita Freitas, Tiago Barroso, Sofia Braga, Catarina C Santos, Marta Batista, Andreia Chaves, Sara Cabral, Ana Fortuna, Vanessa Patel, João Araújo, Tânia Duarte, Tiago P Cabral, Sandra Silva, Cláudia Viana, Carlota Baptista, Joana Gonçalves, Inês Q Dunões, Inês Eiriz

Published in

Cureus. Volume 18. Issue 5. Pages e109017. Epub May 17, 2026.

Abstract

The treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) (ribociclib, palbociclib, and abemaciclib) combined with endocrine therapy (ET) has become the standard of care (SoC) for first-line treatment in patients with metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. There is a lack of consensus on what treatment to offer after disease progression, and there are no established guidelines for therapeutic sequencing.
This multicentric retrospective observational analysis aims to characterize systemic treatment following CDK4/6i, among patients with HR+/HER2- metastatic breast cancer (MBC).
An observational retrospective study performed in 10 Portuguese oncological centers evaluated 237 patients with MBC who had been treated with at least one CDK4/6i, between January 2016 and July 2022, and had progressed with this treatment. We collected data on the initial staging, the date of diagnosis, HR status, Ki67 and HER2, the date of recurrence, metastatic site, the type of treatment, the date of initiation and the date of progression, and the reason for interruption.
Rechallenging with a different CDK4/6 inhibitor demonstrated the highest overall survival (OS), though it is used in a small percentage of patients, highlighting a potential survival advantage and the need for further investigation into optimal sequencing strategies. While capecitabine showed favorable progression-free survival (PFS) and overall survival, ET alone provided a higher OS, reflecting the influence of disease phenotype and treatment selection. Paclitaxel's shorter survival outcomes likely indicate its use in patients with aggressive disease or visceral crisis. These findings underscore the variability in survival outcomes based on post-CDK4/6i therapy choices in HR+/HER2- MBC, with promising evidence for rechallenging strategies.
 Switching CDK4/6i and ET conferred a statistically significant improvement of PFS in patients with progression or recurrence on prior CDK4/6i-containing therapy. These findings underscore the variability in survival outcomes based on post-CDK4/6i therapy choices in HR+/HER2- MBC, with promising evidence for rechallenging strategies.

PMID:
42311745
Bibliographic data and abstract were imported from PubMed on 18 Jun 2026.

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