Verzenio (abemaciclib) / Eli Lilly - LARVOL DELTA

ABIGAIL: ABemaciclib, ET ± paclItaxel in aGgressive HR+/HER2- MBC trIaL (clinicaltrials.gov) - P2 | N=162 | Completed | Sponsor: MedSIR | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Renal adverse events associated with cyclin-dependent kinase 4/6 inhibitors. (PubMed, Cancer Treat Rev) - "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."

Adverse events • Journal • Review • Acute Kidney Injury • Breast Cancer • Cardiovascular • Fibrosis • Heart Failure • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Hypertension • Immunology • Nephrology • Oncology • Renal Disease • Solid Organ Transplantation • Solid Tumor • Transplantation • CST3 • HER-2

Neoadjuvant Abemaciclib plus Letrozole vs. Chemotherapy in patients with HR+/HER2- Highly Proliferative Breast Cancer. (PubMed, Clin Cancer Res) - "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."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety of abemaciclib plus endocrine therapy versus endocrine therapy alone in HR + and HER2-negative breast cancer; a systematic review and meta-analysis. (PubMed, Breast Cancer Res Treat) - "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."

Clinical • Journal • Retrospective data • Review • Breast Cancer • Cardiovascular • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Leukopenia • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Solid Tumor • Thrombocytopenia • HER-2

Risk of venous thromboembolism associated with CDK 4/6 inhibitors and adjuvant hormonal therapy in non-metastatic breast cancer: A systematic review and meta-analysis (ASH 2025) - "More recently, the Introduction of cyclin-dependentkinase 4 and 6 (CDK 4/6) inhibitors, Abemaciclib, Palbociclib, and Ribociclib, has led to new treatment forhigh-risk patients...The comparator group in thisanalysis consisted of patients treated with endocrine therapy alone with aromatase inhibitors (AI),tamoxifen, or fulvestrant... Results from this study show that for adult patients with local and locally advanced breastcancer, there is increased risk of VTE development when treated with CDK 4/6 inhibitors compared totreatment with endocrine therapy alone. Limitations to this analysis include exclusion of metastaticdisease, limited data available on mortality associated with VTE incidence, and varying degrees of patient-specific thromboembolic risk factors. As the use of CDK 4/6 inhibitors in the treatment of breast cancergrows, this information will provide further information for conversations about risks and benefits whenselecting treatment plans."

Metastases • Retrospective data • Review • Breast Cancer • Chronic Kidney Disease • Genetic Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Respiratory Diseases • Solid Tumor • Venous Thromboembolism • HER-2

The combination of ruxolitinib and the CDK4/6 inhibitor abemaciclib demonstrates safety and efficacy in previously treated myelofibrosis patients: Results of A phase I study (ASH 2025) - P1 | "Prior treatments included RUX plus pelabresib/placebo (n=3),hypomethylating agents (n=2), hydroxyurea (n=2), stem cell transplant (n=1). Combination therapy with RUX and the CDK 4/6 inhibitor ABE is safe and has encouragingobjective evidence of efficacy among pts with advanced, previously treated MF, confirming preclinicalhypotheses. These data nominate combined JAK and CDK4/6 inhibitor strategies for future investigationin JAK-STAT driven diseases. The combination of RUX and ABE will now advance to a phase II study inpreviously treated MF patients."

Clinical • P1 data • Breast Cancer • Fibrosis • Immunology • Myelofibrosis • Neutropenia • Solid Tumor • Thrombocytopenia • CALR • CDC25A • GNRP • JAK2

Cyclic kinase 4 and 6 inhibitor plus endocrine therapy (ET) as first-line therapies in advanced breast cancer: A patient-level data network meta-analysis (ESMO Asia 2025) - "In the first-line setting for HR+/HER2− advanced breast cancer, all CDK4/6 inhibitors combined with endocrine therapy significantly improve progression-free survival compared with endocrine therapy alone, with no significant differences observed among them."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Effectiveness and safety of ribociclib versus abemaciclib in the management of HR-positive and HER2-negative metastatic breast cancer: A multi-center retrospective cohort in Saudi Arabia (ESMO Asia 2025) - "Patients with a history of prior use of CDK 4/6 inhibitors or concomitant use of Tamoxifen with Ribociclib were excluded. Of 318 screened patients, 142 met the inclusion criteria. This study concludes that Abemaciclib and Ribociclib demonstrate comparable PFS, with safety profiles consistent with those reported from MONALEESA and MONARCH trials. Notably, hyperkalemia was identified as a potential adverse event not previously reported in the literature."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A retrospective observational study of abemaciclib safety and effectiveness in patients with breast cancer in China (ESMO Asia 2025) - "This study is the largest real-world abema safety study in China to date. Abema was well-tolerated, with low prevalence of AEs of interest, and effectiveness results were consistent with prior trials, across menopausal status groups, disease settings, and regardless of endocrine therapy partner. These results confirm that the real-world benefit-risk profile of abema is positive among Chinese pts with BC."

Observational data • Retrospective data • 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

Patterns of clinical utilization and outcomes of abemaciclib (abema) among hormone receptor+, human epidermal receptor 2- (HR+, HER2-) advanced breast cancer (ABC) patients in China (ESMO Asia 2025) - "In this large-population real-world study, the majority of patients initiated abema per label. Dose adjustment was a practical approach to managing adherence in clinical practice."

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

Efficacy of abemaciclib following progression on prior CDK4/6i in HR+/HER2- metastatic breast cancer: Real-world experience in Moscow (ESMO Asia 2025) - "Of these, 23 patients had previously progressed on first line palbociclib (n=12) or ribociclib (n=11) and were subsequently treated with abemaciclib plus fulvestrant. Median age was 62 years (range: 31–88). Our real-world data support the use of abemaciclib after progression on other CDK4/6i. The observed clinical benefit is consistent with previously published data from the postMONARCH study and other retrospective series. Sequential use of CDK4/6i may be a valuable treatment strategy for selected patients with sustained endocrine sensitivity, delaying the need for chemotherapy."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Concomitant use of proton pump inhibitors and palbociclib or abemaciclib in patients with endocrine-sensitive advanced breast cancer: A multicenter retrospective study (ESMO Asia 2025) - "Concomitant PPI use decreased the effectiveness of palbociclib; however, it did not affect the effectiveness of abemaciclib."

Metastases • Retrospective data • Breast Cancer • Oncology • Solid Tumor • CDK4

Molecular interaction of abemaciclib with human serum albumin: Insights from spectroscopy, microscopy, and computational approaches. (PubMed, Int J Biol Macromol) - "Collectively, these findings elucidate the structural and thermodynamic determinants of albumin-drug interactions and provide mechanistic insights into the pharmacokinetics of abemaciclib. This work highlights the significance of albumin binding at the molecular interface, offering implications for dose optimization and albumin-based drug delivery strategies."

Journal

Safety of CDK4/6 inhibitors in older patients: A FAERS-based analysis of serious and fatal adverse events. (PubMed, J Geriatr Oncol) - "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."

Adverse events • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

The potential effects of the synergistic interaction between ferulic acid and new generation CDK inhibitor anti-neoplastic drugs on breast cancer anti-tumour activity. (PubMed, Med Oncol) - "Ribociclib (Ribo) and Abemaciclib (Abe) are new-generation CDK inhibitors approved for use in breast cancer treatment. Some molecular mechanisms were elucidated by revealing the synergistic effect of FA combined with Ribo and/or Abe in both HR positive and HR negative breast cancer and its possible toxicity or protection on normal breast cells. The present findings suggest that FA is a viable candidate for adjuvant or neoadjuvant treatment in combination with Ribo and/or Abe, as an alternative to Letrozole or Fulvestrant, which have been associated with significant adverse effects in clinical settings."

Journal • Breast Cancer • Eye Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • ER

High-Risk Node-Positive Hormone Receptor-Positive/HER2-Low Breast Cancer Relapse on Adjuvant Abemaciclib Treatment with ER Loss at Metastatic Recurrence: A Case Report and Literature Review. (PubMed, Diagnostics (Basel)) - "Conversely, T-DXd administered due to the presence of HER2-low showed excellent effectiveness. Performing a re-biopsy is crucial due to the possible loss of estrogen receptors, which would require a change in therapeutic strategy no longer based on endocrine therapy. In cases that remain luminal, knowledge of the mutational profile may help to offer patients novel targeted treatments."

Journal • 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 • Triple Negative Breast Cancer • ER • HER-2 • RB1

Clinicogenomic Features of Recurrence After Adjuvant Abemaciclib in HR+/HER2- Early Breast Cancer (SABCS 2025) - "Median duration of abemaciclib therapy was 12.6 months (0.5-34.6); discontinuation was due to disease progression (14; 77.8%), toxicity (2; 11.1%), therapy completion (1; 5.6%), or early switch to olaparib (1; 5.6%). In this cohort, recurrence after adjuvant abemaciclib occurred in 5.4% of patients and was characterized by frequent hormone receptor loss and enrichment of alterations associated with endocrine and CDK4/6 inhibitor resistance, including RB1, PTEN, and MYC, as well as targetable alterations such as PIK3CA and BRCA2. These findings highlight the potential value of molecular profiling earlier in the treatment course to assess risk of relapse in high-risk early-stage disease. Updated data will be presented at the meeting."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA2 • ER • HER-2 • PALB2 • PIK3CA • PTEN • RAD51D • RB1

Current and future use of oral selective estrogen receptor degraders (SERDs) in the management of ER-positive (ER+), HER2-negative (HER2-neg) metastatic breast cancer (mBC): A survey of 20 breast cancer research leaders (RLs) (SABCS 2025) - "Background: The Jan 2023 approval of elacestrant (E) for patients with ER+ HER2-neg mBC and an ESR1 mutation (ESR1mut) with disease progression (PD) on endocrine therapy introduced new considerations for biomarker-guided decision-making. RLs have rapidly incorporated E into the management of progressive ER+ HER2-neg ESR1mut mBC, but the decision to employ this agent appears to be heavily influenced by the global disease burden and the duration of benefit from first-line treatment. Most RLs consider the newly approved imlunestrant largely equivalent to E, and all would also consider its use in combination with abemaciclib in certain situations. Many fewer would use camizestrant for patients found to have an ESR1mut without clinical PD, but an important and significant minority believe this option should be available to select patients."

Metastases • 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 • ER • HER-2 • PIK3CA

A randomized phase II study to evaluate the efficacy and safety of Trastuzumab deruxtecan (T-DXd) versus CDK4/6 inhibitor-based endocrine therapy as first-line therapy of hormone receptor-positive (HR+) and HER2-low/ultralow advanced breast cancer (ABC) patients classified as non-luminal subtype according to gene expression profiling: the PONTIAC study (SABCS 2025) - P2 | "Moreover, pts treated with a CDK4/6 inhibitor in the adjuvant setting with a treatment-free interval ≥ 12 months following CDK4/6 inhibitor treatment completion are allowed.Pre-screening central PAM50 analysis will be conducted in endocrine-resistant pts and in endocrine-sensitive pts who meet at least one of the following criteria: estrogen receptor expression ≤ 50% or presence of liver metastases, or high histological grade or Ki67 > 50% in the primary tumor or known non-luminal subtype as per local PAM50 analysis.Pts will be randomized 1:1 to either T-DXd (5.4 mg/kg intravenously once every 3 weeks) or endocrine therapy (fulvestrant or an aromatase inhibitor ± GnRH analogs for men and pre-/perimenopausal women) plus investigator's choice of CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib). Pts-reported outcomes and safety will be analyzed descriptively. Target enrollment is 200 pts, and initial patient enrollment is anticipated to begin in..."

Clinical • Gene expression profiling • Metastases • P2 data • 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 • ER • HER-2

Efficacy of systemic therapy in HER2-low breast cancer with CNS metastases: a "real-world" experience (SABCS 2025) - "Systemic therapies for the CNS disease included cytotoxic chemotherapy in seven patients (44%), trastuzumab deruxtecan (T-DXd) in four (25%), abemaciclib in two (13%), other CDK4/6 inhibitors in two (13%), and sacituzumab govitecan in one (6%). Commonly utilized chemotherapy included taxanes (paclitaxel or nab-paclitaxel) in 4 of 7 patients... This "real-world" experience highlights modest intracranial activity of systemic therapy in HER2-low breast cancer with CNS metastases. Although response rates were lower than in HER2-positive counterparts, HER2 2+ tumors and patients treated with T-DXd showed encouraging outcomes. These findings support the need for prospective studies focusing on HER2-low CNS disease and suggest T-DXd as a promising therapeutic option, even in the absence of concurrent local treatment."

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

Retrospective study evaluating eligibility, treatment patterns, and clinicopathologic factors associated with adjuvant abemaciclib use in patients with high-risk estrogen receptor-positive (ER+) HER2-negative (HER2-) early breast cancer (EBC) (SABCS 2025) - "13 (25.5%) pts were offered but declined abema, 4 (7.8%) were lost to follow-up, 3 (5.9%) started ribociclib. Other reasons: comorbidity+age (n=4, 7.8%), ≥3 comorbidities (n=1, 2%), severe comorbidity (n=2, 3.9% [Crohn's disease and psychiatric disorder]), poor ET tolerance (n=2, 3.9%), ongoing olaparib (n=1, 2%), metastatic disease at post-surgical staging (n=1, 2%), pt hesitation despite abema prescription (n=2, 3.9%)... In this cohort, a gap between EAT and ENT pts was seen. Older age and lower nodal burden were associated with not receiving adj abema. Pt choice and comorbidities also contributed to non-initiation."

Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Randomized open-label multicenter phase 2 trial comparing first-line olaparib versus CDK4/6 inhibitor plus endocrine therapy in patients with gBRCAmut-associated HR+/HER2- advanced breast cancer [BR21-08, OPERA trial] (SABCS 2025) - "Six patients received CDK4/6i+ET (2 ribociclib, 2 abemaciclib, 2 palbociclib) and 3 received olaparib as first-line therapy. In gBRCAmut HR+/HER2- ABC, first-line olaparib demonstrated numerically longer PFS and a favorable safety profile compared with CDK4/6i plus ET. These findings should be interpreted with caution given the small sample size."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • HER-2 • HRD

Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax. (PubMed, Res Sq) - "We report that ONC201 and highly potent second generation ClpP agonists (TR-57, TR-107), promote induction of senescence in triple-negative breast cancer (TNBC) cell lines...By contrast, cells treated with the cell cycle inhibitor and senescence inducer, abemaciclib rapidly regained p-Rb and Myc expression and cell proliferation following washout...Combining a ClpP agonist with a PARP inhibitor (olaparib) produced an additive effect. In summary, we show that ClpP activators stably induce an irreversible senescence in a ClpP-dependent manner that synergizes with venetoclax in TNBC cells."

IO biomarker • Journal • Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • CHEK2 • LMNB1 • MYC • TP53BP1

An atlas of ex vivo drug sensitivity profiles in 666 clinical glioblastoma samples revealed distinct survival-associated networks (SNO 2025) - P=N/A | "Eleven drugs were tested, including DNA-damaging agents (lomustine, carboplatin, temozolomide, procarbazine, irinotecan, etoposide) and targeted agents (abemaciclib, dabrafenib, osimertinib, rucaparib, trametinib). Longitudinal sampling revealed dynamic changes in drug sensitivity, reflecting evolutionary tumor biology. This ex vivo drug sensitivity atlas reveals distinct, non-random survival-associated clustering patterns that reflect underlying glioblastoma cellular physiologies and may inform future clinical trial designs."

Preclinical • Brain Cancer • Glioblastoma • Glioma • Solid Tumor

Emerging Targeted Therapies and Ongoing Clinical Trials in Pediatric Brain Tumors (PubMed, No Shinkei Geka) - "Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus..."

Journal • Review • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • High Grade Glioma • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • BRAF • KIAA1549 • NF1 • NTRK