Kisqali (ribociclib)

This study confirms first-line CDK 4/6i effectiveness, with abemaciclib and ribociclib showing prolonged PFS vs. palbociclib. This study could not confirm a ranking of the three CDK 4/6i.

P1/2, N=74, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Apr 2025 --> Nov 2025

P3, N=1684, Active, not recruiting, West German Study Group | Recruiting --> Active, not recruiting

P3, N=500, Recruiting, American Society of Clinical Oncology | Not yet recruiting --> Recruiting

Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

Mechanistically, inhibition of activin receptor-like kinase 1 signaling increased key restriction point mediators, and treatment with the CDK4/6 inhibitors palbociclib or ribociclib blocked increases in pRB1 and retinal AVMs in HHT mice. Endothelial cell-specific deletion of CDK6 was sufficient to protect HHT mice from AVM pathology. Thus, clinically approved CDK4/6 inhibitors might have the potential to be repurposed for HHT.

P1, N=34, Recruiting, University of Utah | Trial primary completion date: Aug 2024 --> Apr 2024

P2, N=200, Recruiting, Oana Danciu | Active, not recruiting --> Recruiting

This study highlights that patients with MCV delta > 10 had longer median progression-free survival compared to those with MCV delta ≤ 10.

P2, N=190, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P1, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Sep 2024 --> Apr 2025

With longer follow-up and most patients off ribociclib, NATALEE continues to demonstrate iDFS benefit with ribociclib plus NSAI over NSAI alone in the overall population and across key subgroups. Observed adverse events remained stable.

The findings of this paper demonstrate a significant improvement in iDFS when ET is combined with CDK4/6i, compared to ET alone. Specifically, treatments with abemaciclib and ribociclib showed notable enhancements in dRFS.

Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. A higher discontinuation rate for abemaciclib was reported in patients aged ≥65 years and it can be assumed that discontinuation rates may increase in even older patients. If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population.

P2, N=376, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P4, N=137, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2030 --> Feb 2028 | Trial primary completion date: Feb 2030 --> Jan 2028

P1/2, N=37, Recruiting, Kari Wisinski | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

Differences in specific cell infiltration can lead to increased sensitivity of the immune-inflamed subgroup to anti-tumor drugs. The proposed lncRNA model holds great promise to assess the immune landscapes and therapeutic reactions of TNBC patients.

P3, N=500, Recruiting, AstraZeneca | Trial completion date: Jul 2030 --> Oct 2030

P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Aug 2024 --> Nov 2024

In real-world settings, and away from the stringency of controlled clinical trials, endocrine therapy in combination with ribociclib in patients with HR-positive/HER2-negative MBC is an effective and well-tolerated therapy with a manageable toxicity profile and a low drug discontinuation rate. Dose reduction due to toxicity did not worsen the outcome.

P=N/A, N=328, Not yet recruiting, Novartis Pharmaceuticals

P3, N=504, Not yet recruiting, Danish Breast Cancer Cooperative Group | Phase classification: P4 --> P3 | N=250 --> 504

P1, N=155, Recruiting, Olema Pharmaceuticals, Inc. | N=90 --> 155 | Trial completion date: Aug 2024 --> Jun 2026 | Trial primary completion date: Aug 2024 --> May 2026

P1, N=30, Suspended, University of Michigan Rogel Cancer Center | Recruiting --> Suspended

P=N/A, N=194, Completed, Novartis Pharmaceuticals

P1/2, N=255, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.

Both Ribociclib and palbociclib have similar CBR, PFS and toxicity profile.

Our study provides the RWD with the use of CDK4/6 inhibitors in the treatment of metastatic HR+/HER2- breast cancer. To our best knowledge, there are limited RWD regarding CDK 4/6 inhibitors use in western Balkan; thus, our study provides valuable data from everyday clinical practice for this region of Europe, bridging the gap between randomized clinical trials and clinical reality in western Balkan.

P3, N=312, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

P2, N=200, Active, not recruiting, Oana Danciu | Recruiting --> Active, not recruiting

Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments.

This analysis identified acquired gene alterations in patients with HR+/HER2- advanced breast cancer treated with ribociclib plus ET or placebo plus ET. These data may support further studies on acquired resistance mechanisms and inform future systemic interventions in the post-CDK4/6 inhibitor setting.

P2, N=100, Recruiting, Nationwide Children's Hospital | Not yet recruiting --> Recruiting

Many women with EBC will qualify for adjuvant CDK4/6 inhibitors (17.5% abemaciclib, 41.3% ribociclib) with resource and workforce implications. In the real-world setting, a greater proportion of adjuvant CDK4/6-eligible patients have lower stage disease, therefore the absolute benefit from treatment may be smaller than estimated by the trials.

P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> Apr 2025 | Trial primary completion date: Dec 2024 --> Apr 2025

P1/2, N=74, Active, not recruiting, Novartis Pharmaceuticals | N=346 --> 74

P=N/A, N=286, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2- ABC, which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.

Palbociclib was associated with QTc prolongation, however, the RR for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class.

Compared with aromatase inhibitor (AI), palbociclib plus AI (PalboAI) exhibited a significantly longer PFS up to the 36th month of follow-up [HR=1.7; 95% credible interval, 1.36-2.16], including on the 3rd [OR=2.22; 95% confidence interval (CI), 1.10-4.47], 6th (OR=2.39; 95% CI, 1.21-4.69), 12th (OR=1.94; 95% CI, 1.34-2.79), 18th (OR=2.38; 95% CI, 1.65-3.44), 24th (OR=2.39; 95% CI, 1.67-3.43), 30th (OR=2.10; 95% CI, 1.62-2.74) and 36th (OR=2.66; 95% CI, 1.37-5.18) month of follow-up. Additionally, abemaciclib plus fulvestrant exhibited significant effects compared with AI alone between 12 and 36 months. Ribociclib plus fulvestrant, ribociclib plus AI and dalpiciclib plus AI exerted significant effects compared with AI alone between 12 and 30 months. Considering the effect on OS and PFS together with adverse reactions, safety, medical compliance and route of administration, PalboAI was found to be the optimal treatment for HR+/HER2-mBC. However, additional head-to-head clinical trials are warranted to confirm these findings.