Kisqali (ribociclib) / Otsuka, Novartis - LARVOL DELTA

Targeting Mitochondrial Metabolism and Treatment Resistance in PancreaticCancers (ENDO 2025) - "To assess the hypothesis that combination of JD006 biguanide analogues with CDK 4/6 and CDK2/4/6 inhibitors could improve treatment outcomes for PDAC, we combined JD006 with CDK4/6 inhibitors (abemaciclib, ribociclib) or CDK2/4/6 inhibitor PF0687300 in preclinical PDAC models (Panc-1, MIA Paca-2, CFPac). These findings suggest that more potent biguanides combined with CDK inhibitors may provide a new therapeutic strategy for PDAC, addressing both the disease's molecular drivers and health disparities in affected populations. Further study is needed to explore the molecular signatures and responses in patients of diverse ancestries to optimize clinical outcomes."

Diabetes • Metabolic Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Type 2 Diabetes Mellitus • CDKN2A • KRAS

Targeting Mitochondrial Metabolism and Treatment Resistance in PancreaticCancers (ENDO 2025) - "To assess the hypothesis that combination of JD006 biguanide analogues with CDK 4/6 and CDK2/4/6 inhibitors could improve treatment outcomes for PDAC, we combined JD006 with CDK4/6 inhibitors (abemaciclib, ribociclib) or CDK2/4/6 inhibitor PF0687300 in preclinical PDAC models (Panc-1, MIA Paca-2, CFPac). These findings suggest that more potent biguanides combined with CDK inhibitors may provide a new therapeutic strategy for PDAC, addressing both the disease's molecular drivers and health disparities in affected populations. Further study is needed to explore the molecular signatures and responses in patients of diverse ancestries to optimize clinical outcomes."

Diabetes • Metabolic Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Type 2 Diabetes Mellitus • CDKN2A • KRAS

The Modulatory Effects of Statins, Vitamin E, and Moringa Oleifera Extract on CD3 Expression in Ribociclib-Induced Hepatotoxicity in Rats. (PubMed, Acta Inform Med) - "Treatment with statin and vitamin E lowered the expression of CD3, but this was not statistically significant (p>0.05), while the treatment with Moringa Olifera extract lowered significantly the expression of CD3 in the liver (p=0.043). Giving Statin, Vitamin E, or Moringa Olifera extract can protect the liver from the liver toxicity that ribociclib causes."

Journal • Preclinical

Predictive effect and clinical diagnosis significance of exosome-related genes for nonalcoholic fatty liver disease-related hepatocellular carcinoma. (PubMed, Sci Rep) - "Furthermore, patients in the high-risk group were more sensitive to chemotherapy drugs such as 5-Fluorouracil, Leflunomide, Cisplatin, ML323, Dabrafenib, Palbociclib, Irinotecan, Ribociclib and Nilotinib. In summary, our study clarified the predictive effect and clinical diagnosis significance of exosome-related genes in the development of NAFLD-related HCC and provided new directions for the prognosis of NAFLD-related HCC patients."

Biomarker • IO biomarker • Journal • Addiction (Opioid and Alcohol) • Hepatocellular Cancer • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • CD4 • PD-1 • PD-L1 • PD-L2 • VAMP5

Real-World Data on First-Line Treatment of Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer in Brazil (BRAVE Study). (PubMed, Clin Breast Cancer) - "ET remains the most used first-line treatment in Brazil. However, access to therapies varies significantly between public and private healthcare sectors. This disparity highlights inequality in access to treatment."

Journal • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

HEALING TURNED HARMFUL: RIBOCICLIB-INDUCED ORGANIZING PNEUMONIA (CHEST 2025) - No abstract available

Infectious Disease • Pneumonia

21 Distant Disease-Free Survival Across Key Subgroups From the Phase 3 NATALEE Trial of Ribociclib Plus a Nonsteroidal Aromatase Inhibitor in Patients With HR+/HER2− Early Breast Cancer (Cancer Network) - P3 | N=5,101 | NATALEE (NCT03701334) | Sponsor: Novartis Pharmaceuticals | "At the data cutoff of April 29, 2024 (median duration of follow-up for DDFS, 44.2 months, all patients off ribociclib), ribociclib plus NSAI demonstrated a DDFS benefit (HR, 0.715; 95% CI, 0.604-0.847; nominal P value <.0001) and a distant recurrence-free survival benefit (HR, 0.705; 95% CI, 0.589-0.844; nominal P value <.0001) in the intent-to-treat population. The DDFS benefit was consistent regardless of the anatomic stage. The absolute DDFS benefit with ribociclib plus NSAI vs NSAI alone increased from 3 years to 4 years for all stage subgroups. Similarly, a consistent improvement in DDFS was observed regardless of nodal status, and the absolute DDFS benefit increased from 3 years to 4 years across nodal subgroups."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

BREAKER-101: Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=392 | Recruiting | Sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) | N=153 ➔ 392

Enrollment change • Breast Cancer • Colorectal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Oncology • Solid Tumor • KRAS

Identifying on-target and off-target effects of hundreds of oncology drugs in PRISM large-scale cell line profiling with machine learning analysis of baseline and functional genomic features (EACR 2025) - "Material and Over 200 drugs, including encorafenib, dabrafenib, pevonedistat, palbociclib, ribociclib, abemaciclib, docetaxel and paclitaxel were screened across ~900 PRISM cell lines at 8 point dose in triplicate. Our findings establish the OncRef dataset and PRISM as a benchmark for evaluating current and emerging cancer therapies. Using large-scale systematic PRISM cell line profiling, genomic characterization and machine learning analysis enables better characterization of oncology drugs and will potentially reduce clinical trials failures."

Machine learning • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A genetic signature predicts the response of aggressive paragangliomas to dual PI3K and CDK4/6 inhibition. (EACR 2025) - "In this study, we investigate the antitumor potential of targeting two key dysregulated pathways in PPGL: PI3K signaling and cell cycle regulation.Material and We assessed the efficacy of buparlisib, a PI3Kα inhibitor (PI3Ki), and ribociclib, a CDK4/6 inhibitor (CDK4/6i), as monotherapies and in combination, using functional assays in representative in vitro models of PPGL. Combined inhibition of PI3K and CDK4/6 targets mitotic spindle regulation and exerts potent antitumor effects in PPGL models. Given the upregulation of mitosis-associated genes in mPPGL, this combination therapy holds promise as a novel approach for treating aggressive forms of these tumors."

Oncology • Solid Tumor • FOXM1 • PIK3CA

Real-World Outcomes of Ribociclib Treatment in Patients With Metastatic Breast Cancer at a Tertiary Care Hospital. (PubMed, Cureus) - "The most common adverse effect was neutropenia (68%), which was manageable with appropriate dose reductions. Conclusion Our retrospective data support the notion that ribociclib-based therapy is effective and safe in patients with HR+/HER2- ABC/MBC; however, as it is a retrospective study with a small sample size, further prospective studies are necessary to further prove these results in the local population, and efforts should be taken in society at large to make this treatment available to all patients who require this treatment."

Journal • Real-world evidence • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2) (clinicaltrials.gov) - P3 | N=674 | Recruiting | Sponsor: Celcuity Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Letter Re: A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial. (PubMed, Ann Oncol) - No abstract available

Journal • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Health Canada approves Novartis' KISQALI for HR+/HER2- early breast cancer patients at high risk of recurrence (Canada Newswire) - "Novartis Canada is pleased to announce that Health Canada has granted a Notice of Compliance (NOC) for KISQALI (ribociclib tablets) in combination with an aromatase inhibitor (AI) for the adjuvant treatment of adult patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) stage II-III early breast cancer (eBC) at high risk of recurrence....The Health Canada approval is based on the global Phase III NATALEE trial, which included a broad patient population with HR+/HER2- stage II and III eBC. At the final analysis, this clinical trial demonstrated a statistically significant and clinically meaningful reduction in the risk of disease recurrence with ribociclib plus AI compared to AI alone."

Canada approval • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Free lecture: Travel Time-Associated Time toxicity of Endocrine-Based Oral CDK4/6 Inhibitor Therapies (DGS 2025) - "Material and eligible patient for ribociclib or abemaciclib therapy were retrospectively identified from 3,776 EARLY Breast Cancer Cases at the University Hospitals of Ulm, Lübeck, and Tübingen Using The Monarche and Natalee Criteria (Ulm/Tübingen: 2018–2020; Lübeck: 2013–2023). This analysis, Despite Its Hypothetics Limitations, Provides Valuable Into the Impact of Centralized Care on Travel Time and Co₂ emissions For oral cancer therapy in Germany. As the use of oral therapies increate, future discussions should focus on reducing the time burden through strategies like shared care models between Local Gynecologists and Cancer Centers, To Enhance Care Quality."

Breast Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor

Hepatotoxicity across CDK 4/6 inhibitors: a Narrative Review. (PubMed, Support Care Cancer) - "Twenty-five systematic reviews and meta-analyses, RCTs, pooled safety analysis and observational studies were included in this narrative review to evaluate the incidence rate of palbociclib, ribociclib and abemaciclib induced hepatoxicity. Ribociclib seems to be associated with the highest risk of drug-induced hepatotoxicity. More studies need to be done to confirm and quantify this finding."

Clinical • Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Indirect Comparison Suggests Ribociclib Combined with non-steroidal aromatase inhibitors is significant more effective Than Tamoxifen in Prememenopausal Women with Early Breast Cancer (DGS 2025) - P3 | "Ribociclib+NSAI+OFS Proved Beneficial Across All Effective Endpoints Compared to Tamoxifen ± ofs. The results highlight that ribociclib is a promising, effective and well-tolerated treatment option for impemenopausal patients with HR+/Her2- EBC."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Navigating the Limits of Ribociclib in Early Breast Cancer: Questions from the NATALEE Trial. (PubMed, Ann Oncol) - No abstract available

Journal • Breast Cancer • Oncology • Solid Tumor

PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1 IS A KEY METABOLIC REGULATOR AND POTENTIAL THERAPEUTIC TARGET IN LYMPHOMA (ICML 2025) - "PDPK1 was pharmacologically inhibited by GSK2334470...PDPK1 inhibition was associated with cell cycle arrest in G1 phase of the cell cycle and was in vitro broadly synergistic with unspecific standard anti-lymphoma chemotherapeutics (doxorubicin, vincristine, and cisplatin) and highly synergistic with more targeted CDK4/6 inhibitor ribociclib... PDPK1 seems to be critically involved in AKT pathway activation and metabolism regulation in lymphoma and may represent an universal and effective therapeutic target."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MAP2K1 • MYC • PDPK1 • PIK3CD • PTEN

Formerly breast cancer: How many patients are potential candidates of a combined endocrine therapy? (DGS 2025) - "Objective: This retrospective case evaluation evaluates the number of potential candidates for combined endocrine therapy (Olaparib, Abemaciclib and Ribociclib) in the Real-World Context. The broad indication criteria of the Natale study could increase the workload in the clinic, since more frequent doctor-patient interactions are required. However, it remains unclear how therapy recommendations affect actual treatment, as increased visits and potential side effects could affect the compliance of patients."

Clinical • Breast Cancer • Oncology • Solid Tumor

Hepatotoxicity in Patients Undergoing Systemic Treatment with Ribociclib (DGS 2025) - "7/9 PTS Continued with Abemaciclib, Without Further Relevant Liver toxicity. Therapy with Riboclib Treatment Cause Liver Enzyme Elevation What Might Require Treatment Discontinuation. Therapy with Riboclib Treatment Cause Liver Enzyme Elevation What Might Require Treatment Discontinuation. Further Studies are Planned to investigate the underlying mechanism, possible risk factors and the role of corticosteroid in the clinical management. At the congress we will present a Further Update of the Cohort Treated with Ribociclib."

Clinical • Breast Cancer • Hepatocellular Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Early non-compliance with oral anticancer drugs, a clinical pharmacy as key issue in onco-senology (PubMed, Therapie) - "More than half the patients in our cohort appear to be poorly compliant at an early stage, whatever the assessment score. This assessment of compliance constitutes a feasibility study for the use of our questionnaire in routine clinical monitoring of patients receiving an OAC."

Compliance • Journal • Breast Cancer • Oncology • Oral Cancer • Solid Tumor

How to choose optimal adjuvant therapies for high-risk hormone receptor-positive, HER2-negative breast cancer after chemotherapy? (PubMed, Acta Oncol) - "Optimal patient selection for these often toxic treatments remains partially unclear and is the focus of intensive research. In the near future, monitoring ctDNA may enable treatment de-escalation for selected high-risk patients. The rise of perioperative immunological therapies, new CDK4-specific inhibitors, and targeted endocrine treatments can lead to a notably favorable prognosis for many previously high-risk HR+/HER2- breast cancers. Future research should prioritize predictive biomarkers and personalized approaches to optimize treatment efficacy, ensure more equal access to treatments, and minimize overtreatment."

Journal • Review • Breast Cancer • Endocrine Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • HER-2

Rethinking Ribociclib: Revisiting Dosing, Duration, and the N0 High-Risk Dilemma in the NATALEE Trial. (PubMed, Ann Oncol) - No abstract available

Journal

Comment on Medicine Access Programmes: what do patients think - a patient-reported outcome study on ribociclib in metastatic breast cancer in Australia. (PubMed, Intern Med J) - No abstract available

Journal • Breast Cancer • Oncology • Solid Tumor