Kisqali (ribociclib)

Moreover, dalpiciclib is being investigated in HR+/HER2- BC treatment. This article will summarize clinical efficacy, recommendations, and differences in toxicity profile between palbociclib, ribociclib, and abemaciclib and will also discuss the possibility of using dalpiciclib in the treatment of breast cancer.

P1/2, N=256, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2025 --> Dec 2025

Patients receiving ribociclib or palbociclib were evaluated for the development of ILD. The incidence of CDK4/6 inhibitor-associated ILD in Turkish breast cancer patients appears higher than previously reported in clinical trials. More robust, long-term studies are necessary to identify potential risk factors and mitigate ILD-related mortality.

Elevated TK1 activity after six months of CDK4/6i and an increase in TK1 concentration from baseline to six months under CDK4/6i significantly correlated with a decreased PFS. These results indicate a possible value of TK1 concentration and activity before and during CDK4/6i for HR+/HER2- mBC patients to guide treatment that warrants further investigation.

Materials and A retrospective analysis of 120 patients with HR+/HER2- MBC treated with ribociclib or palbociclib in combination with letrozole or fulvestrant was performed. In our study, while the mPFS was not statistically significant in both arms, the 3-year OS rate was higher in the ribociclib arm and statistically significant. Our findings were confirmed in randomized studies comparing both agents head-to-head.

We identified 10 M2-like TAM-related prognostic signature genes for BRCA, providing potential therapeutic targets for the treatment of the cancer.

This update included 82 unique studies, 42.7% for palbociclib, 7.3% for ribociclib, and 3.7% for abemaciclib; 46.3% assessed multiple CDK4/6i. These data are important to guide clinical decision-making, as they include patients who are not adequately represented in clinical trials. Studies with longer follow-up are needed to assess long-term benefits of all three CDK4/6i therapies in HR+/HER2- A/MBC.

The introduction of the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors abemaciclib and ribociclib to the adjuvant setting marks a significant advancement in the treatment of hormone-receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer (HR+, HER2- EBC). The paper also highlights strategies to enhance patient medication adherence and the involvement of multidisciplinary care teams to support treatment delivery. As research continues to evolve, additional follow-ups of the monarchE and NATALEE trials and future trials will further refine patient selection and treatment sequencing, ultimately improving outcomes and enhancing the quality of life for patients with HR+, HER2- EBC.

We performed adisproportionality analysis to evaluate CDKI-related adverse events (AEs) inolder adults administered abemaciclib, palbociclib, and ribociclib. Our results aligned with clinicalobservations, emphasizing possible CDKI-related AEs. Conducting future clinicalresearch is essential to confirm AE-related differences among CDKIs in olderindividuals.

LOGIC 2 supports the use of encorafenib plus binimetinib for treatment naive and previously treated locally advanced unresectable or metastatic BRAF V600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance.

To improve outcomes, ovarian function suppression (OFS) with gonadotropin-releasing hormone agonists (GnRHa) added to tamoxifen or aromatase inhibitors like exemestane have shown significant disease-free survival (DFS) and, in some cases, overall survival (OS) benefits...Trials with abemaciclib and ribociclib have shown promise in high-risk EBC. For BRCA-mutant patients, the PARP inhibitor olaparib, as demonstrated in the OlympiA trial, significantly improved invasive DFS and OS when used as adjuvant therapy for one year...These advancements reflect a shift toward personalized adjuvant therapy, integrating targeted treatments like CDK4/6 inhibitors and PARP inhibitors, optimizing ET with OFS, and balancing efficacy with quality of life through de-escalation strategies. This tailored approach aims to improve long-term outcomes for HR-positive EBC patients.

P1, N=48, Active, not recruiting, Nader Sanai | Trial completion date: Jan 2025 --> Mar 2026

Therefore, how to screen out the prime population for intensive adjuvant therapy of ribociclib needs to worth explored. In this paper, we discussed that the adaptive neoadjuvant endocrine therapy can screen out the prime population for intensive adjuvant therapy of ribociclib.

P=N/A, N=2615, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P1, N=265, Active, not recruiting, Relay Therapeutics, Inc. | Trial completion date: Jul 2024 --> May 2025 | Trial primary completion date: Jun 2024 --> Mar 2025

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

P3, N=1400, Not yet recruiting, Novartis Pharmaceuticals | N=3100 --> 1400

P=N/A, N=3250, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Here we examine the composition, communication, and phenotypes of tumor-associated cells in serial biopsies from stage II and III high-risk estrogen receptor positive (ER+ ) breast cancers of patients receiving endocrine therapy (letrozole) as single agent or in combination with ribociclib, a CDK4/6-targeting cell cycle inhibitor. Exogenous IL-15 improves CDK4/6 inhibitor efficacy by augmenting T-cell proliferation and cancer cell killing by T cells. In summary, response to ribociclib in stage II and III high-risk ER +  breast cancer depends on the composition, activation phenotypes and communication network of immune cells.

These analyses of NATALEE show that adding adjuvant ribociclib to an NSAI does not negatively impact HRQOL in patients with HR+/HER2- EBC.

Ribociclib with spartalizumab and fulvestrant showed limited efficacy and elevated hepatotoxicity, precluding further development. Correlative analyses revealed treatment-induced immunological effects, and genomic alterations associated with PFS.

Dose reduction had no impact on progression-free survival (PFS) (p = 0.114 for first-line treatment, p = 0.528 for second and subsequent-line treatment; p > 0.05). Regarding the absence of disparity in progression-free survival between patients with dose reduction and those without, dose reduction should not be avoided in certain patient groups to ensure therapy continuity and mitigate potential adverse effects.

Ribociclib, with its broader applicability and impact on the decision making for axillary lymph node surgery, may be the preferred option in high-risk populations. The review also addresses unanswered clinical questions and highlights the need for ongoing research to optimize the adjuvant therapy strategies.

P1, N=6, Terminated, Tvardi Therapeutics, Incorporated | Phase classification: P1/2 --> P1 | Completed --> Terminated; The study was terminated prior to Phase 2 due to slow accrual.

CDK4/6 inhibitors differed in their safety profile reports; for example, neutropenia mainly occurs with palbociclib and ribociclib, diarrhea and venous thromboembolism mainly occur with abemaciclib, and QTc prolongation mainly occurs with ribociclib. Individualized drug administration according to patients' conditions is needed in clinical practice.

Cyclin-dependent kinase (CDK) 4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, are widely used in combination with endocrine therapy for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. The patient developed erythematous, edematous plaques and papules on her hands and forearms, which resolved after discontinuation of the drug and treatment with topical corticosteroids. This report highlights the need for awareness of cutaneous side effects associated with CDK4/6 inhibitors, particularly abemaciclib.

P1/2, N=316, Recruiting, Hoffmann-La Roche | N=510 --> 316

Although objective response rates were modest in this mixed cohort of heavily pretreated patients, ribociclib combined with letrozole or fulvestrant has shown robust PFS and OS in real-world practice. AEs related treatment discontinuation rate is higher than that reported in clinical trials with stringent inclusion criteria.

P1/2, N=400, Recruiting, Stemline Therapeutics, Inc. | Trial completion date: Aug 2026 --> Dec 2028 | Trial primary completion date: Dec 2024 --> Dec 2026

P=N/A, N=3250, Not yet recruiting, Novartis Pharmaceuticals

The concurrent use of CDK4/6 inhibitors and palliative radiotherapy does not increase the incidence of hematological adverse events in patients with metastatic breast cancer.

This study demonstrated that patients prefer adjuvant treatment with higher efficacy and lower risk of adverse events. These data will aid shared decision-making when discussing the addition of CDK4/6is to adjuvant ET for eligible patients with HR+/HER2- EBC.

P1/2, N=510, Recruiting, Hoffmann-La Roche | Trial primary completion date: Apr 2026 --> Nov 2027

P2, N=1100, Recruiting, SOLTI Breast Cancer Research Group | Trial completion date: Jul 2030 --> Dec 2031 | Trial primary completion date: Aug 2028 --> Oct 2029

P1, N=15, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Initiation date: Apr 2024 --> Aug 2024

P=N/A, N=3500, Recruiting, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

After a median follow-up of 144.7 months, 10-year overall survival confirms the prognostic relevance of the inclusion criteria used in pivotal trials. This study provides real-life insights into the prevalence, clinicopathological characteristics and long-term prognosis of HR+/HER2- eBC patients now eligible for adjuvant CDK4/6 inhibitors.

The oncologists provided recommendations on initial assessment and monitoring, follow-up recommendations, and warning signs and symptoms for referral to corresponding specialists based on their experience. The panel of experts also explored clinical scenarios related to each comorbidity and recommended a preferred CDK4/6 inhibitor based on available evidence regarding drug-drug interactions and potential for toxicity.

P1, N=890, Recruiting, Relay Therapeutics, Inc. | N=400 --> 890

P=N/A, N=177, Not yet recruiting, Novartis Pharmaceuticals

This large real-world study suggested that there were no significant OS differences between 1L ribociclib, abemaciclib, and palbociclib in combination with an AI for patients with HR+/HER2- mBC. These findings together with other factors such as safety and quality of life are helpful in the selection of CDK4/6i combination therapy for patients with HR+/HER2- mBC.

This study aims to evaluate the efficacy of ribociclib and palbociclib with ET in HR+/HER2- metastatic breast cancer, addressing the critical gap in understanding treatment outcomes in younger patient populations...Additional factors associated with poorer outcomes included liver metastasis, progesterone receptor negativity, high tumor grade, and the concurrent use of fulvestrant with CDK4/6 inhibitors...The findings underscore the urgent need for personalized treatment strategies, routine genetic testing, and dedicated clinical trials designed to address the specific needs of these high-risk subgroups. By advancing our understanding of the clinical and molecular landscape of early-onset breast cancer and very early-onset breast cancer, this study lays the groundwork for improving outcomes in these underserved patients through tailored therapeutic approaches.