P=N/A, N=100, Enrolling by invitation, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's | Not yet recruiting --> Enrolling by invitation

Omission of SLNB in patients with small HR-positive/HER2-negative tumors results in a missed indication for CDK4/6i in <8 % with minimal impact on recurrence.

The advent of CDK4/6 inhibitors, namely, palbociclib, ribociclib and abemaciclib, has changed the management of oestrogen receptor (ER)-positive/HER2-negative advanced breast tumours. Nonetheless, the acquired resistance to CDK4/6 inhibitors remains a major therapeutic challenge. Thus, the identification of molecular drivers involved in the resistance to these drugs is crucial for the design of novel therapeutic approaches and the selection of patient-centred strategies in various types of tumours.

Clinical data indicate a higher incidence of nephrotoxic adverse reactions in patients receiving CDK4/6i compared to control groups, with abemaciclib showing the highest risk ratio...Preclinical studies suggest a complex effect on renal health; while some data indicate acute nephroprotection, long-term rodent models treated with palbociclib after ischemic AKI demonstrated impaired recovery, increased renal fibrosis, and cellular senescence, indicating potentially detrimental long-term chronic effects...Furthermore, these agents are susceptible to significant drug-drug interactions, particularly with CYP3A4 inhibitors/inducers and immunosuppressants, necessitating careful dose adjustments and monitoring, especially in solid organ transplant recipients. This review consolidates current evidence regarding the renal of CDK4/6i, emphasizing the need for vigilant monitoring and a multidisciplinary approach to optimize patient outcomes.

P2, N=162, Completed, MedSIR | Active, not recruiting --> Completed

P1, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Dec 2026

Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

CARABELA trial results suggest that 12 months of letrozole/abemaciclib may not offer similar efficacy to that of chemotherapy in achieving RCB 0-I. However, in less proliferative tumors (RS <26 or Ki-67 <30%), outcomes were comparable, suggesting that letrozole/abemaciclib could replace (neo)adjuvant chemotherapy in selected patients.

The combination therapy provides a clinically significant improvement in survival and treatment responses, even though the toxicity is increased but manageable, and requires careful prescription.

She was initiated on palbociclib and letrozole treatment in April 2024...She was commenced on ribociclib and letrozole for relapsed metastatic liver disease in April 2023...Understanding the role of CDK4/6 inhibition and the link with psoriasis is important for optimizing therapeutic choices for patients with cancer with pre-existing or newly developed psoriasis. Given the increasing use of CDK4/6 inhibitors in cancer treatment, clinicians should be vigilant of the potential increased prevalence of psoriasis experienced in this patient cohort.

P2, N=144, Recruiting, Hebei Medical University Fourth Hospital | Trial completion date: Dec 2025 --> Dec 2028 | Trial primary completion date: Dec 2024 --> Dec 2026

Real-world data reveal drug- and age-specific toxicity differences. Ribociclib and abemaciclib pose higher risks in older adults compared to palbociclib, supporting the need for personalized treatment and careful monitoring in older patients.