Kisqali (ribociclib)

Early clinical data demonstrated activity of BLU-222, a potent and selective CDK2 inhibitor, both as monotherapy (CCNE1 amplified) and in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. These findings provide evidence that CDK2i combined with CDK4/6i can address multiple known mechanisms of resistance to CDK4/6i, enhancing antitumor responses in preclinical breast cancer models.

P3, N=1000, Recruiting, Olema Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting

CDK4/6 inhibitors have distinct toxicity profiles. Effective AE management and dose adjustments are crucial for maintaining efficacy, emphasizing the need for AE prediction models to optimize CDK4/6i use in HR + HER2 - aBC.

We present a case of a 59-year-old postmenopausal female with metastatic hormone receptor-positive breast cancer who started treatment with fulvestrant and ribociclib after progression on anastrozole...Ribociclib was held, and after no improvement in 28 days, she was treated with a 6-day course of prednisone 1 mg/kg, with significant improvement in her liver enzymes...Following normalization of her liver enzymes, she was rechallenged with abemaciclib with no recurrent hepatotoxicity. Ribociclib hepatotoxicity can be successfully treated with withdrawal of the medication and a short course of corticosteroids if liver enzymes do not improve following a 28-day withdrawal, highlighting a potential immune-mediated mechanism. Additionally, rechallenge with another cyclin-dependent kinase 4 and 6 inhibitor is a safe and effective strategy that should be considered.

This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed.

Ribociclib is associated with an increased risk of hepatotoxicity, with the potential for grade 3-4 in a small number of patients. Our analysis suggested a potential association between grade 3-4 hepatotoxicity and reduced OS, warranting further investigation. Regular monitoring of liver function tests during ribociclib treatment may help clinicians identify high-risk patients requiring closer follow-up.

P1/2, N=792, Recruiting, Hoffmann-La Roche | N=580 --> 792 | Trial completion date: May 2028 --> Sep 2030 | Trial primary completion date: May 2028 --> Sep 2030

Endocrine sensitivity/resistance and ET partner were major determinants of outcome with CDK4/6i plus ET in HR+/HER2- ABC, informing individualized treatment selection and sequencing.

P1, N=50, Terminated, Blueprint Medicines Corporation | Phase classification: P1/2 --> P1 | N=366 --> 50 | Trial completion date: Sep 2026 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2025 --> Jul 2025; This trial was terminated prior to the initiation of Phase 2 for reasons not due to safety concerns.

Ribociclib combined with aromatase inhibitors demonstrated favorable real-world effectiveness and manageable safety profiles in Vietnamese patients with hormone receptor-positive, HER2-negative metastatic breast cancer in a real-world setting.

Materials and This retrospective analysis included 92 patients with HR+/HER2- mBC who received either ribociclib or palbociclib between 2019 and 2024 at a single tertiary care center. Given the potential for confounding by the indication/comorbidity inherent to retrospective studies, the results should be interpreted as associational. These data support the cautious use of non-essential PPIs during ribociclib therapy and underscore the need for prospective agent-specific pharmacokinetic studies.

The CDK4/6is included in this study were palbociclib, ribociclib, and abemaciclib. Treatment with CDK4/6is was not generally associated with worsening HRQoL among patients with MBC, except for the symptom-related, patient-reported measures of diarrhea and upset by hair loss. Understanding HRQoL impacts can help support health care decisions and treatment using CDK4/6is for patients with MBC.