Verzenio (abemaciclib) / Eli Lilly - LARVOL DELTA

Glioblastoma in Appalachia: A retrospective analysis (AACR 2025) - "In the 2nd line setting, no significant differences in PFS or OS were observed between bevacizumab+lomustine (n=7), bevacizumab+surgery (n=9), bevacizumab +temozolomide (n=8), and bevacizumab (n=41)...In the 2nd line targeted therapy setting, no significant differences in PFS or OS were observed between osimertinib (n=2), pembrolizumab (n=2), regorafenib (n=3), and abemaciclib (n=3). Our preliminary data suggests that mortality related to GBM in Appalachia follows the national trends. It is prudent to conduct rural-specific studies to understand the phenotypic, genotypic, and demographic characteristics."

Retrospective data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

Abemaciclib Monotherapy in HR+/HER2- Metastatic Breast Cancer Patients: A Real-World Observational Study in Korea (MonarcKOR) (GBCC 2025) - "In Korean heavily pre-treated patients, real-world outcomes observed with abemaciclib monotherapy in this study appear comparable to those in MONARCH 1, with a numerically more favorable trend. These findings provide valuable initial insights into the efficacy and safety of abemaciclib in Korean patients. The small sample size necessitates cautious interpretation."

Clinical • Metastases • Monotherapy • Observational data • Real-world • Real-world evidence • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

The Investigation of CDK4/6 Inhibitor Usage in HR-Positive, HER2-Negative Advanced/Relapsed Breast Cancer Patients at Our Institution (GBCC 2025) - "From April 2018, 61 patients were prescribed palbociclib (PAL), and from July 2019, 15 patients received abemaciclib (ABE) as first-line CDK4/6i therapy. The most common combination endocrine therapy was fulvestrant (FUL)... This study provides an overview of first-line endocrine therapy with CDK4/6 i in HR-positive, HER2-negative advanced or recurrent breast cancer. Post-first-line treatment strategies varied, with approximately 40% of PAL-treated patients transitioning to ABE. Further research is needed to clarify the optimal sequence of treatments in this patient group."

Clinical • Metastases • Breast Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Infectious Disease • Interstitial Lung Disease • Liver Failure • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • HER-2

Risk Stratification in Early Breast Cancer: Who Truly Benefits from CDK4/6 Inhibition? (Biomarker Driven Approach) (GBCC 2025) - "CDK4/6 inhibitors, such as abemaciclib and ribociclib, have shown promise in improving outcomes for high-risk hormone receptor-positive, HER2-negative EBC. A biomarker-driven strategy for CDK4/6 inhibitor use in EBC holds the potential to optimize treatment, enhance efficacy, and minimize unnecessary exposure to side effects. Future trials should focus on validating predictive biomarkers and refining patient selection criteria to ensure the best possible outcomes."

Biomarker • 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 • CDKN2A • HER-2 • RB1

Endocrine-Resistant Breast Cancer in gBRCA Carriers (GBCC 2025) - "In the early-stage, high risk setting, adjuvant olaparib had demonstrated survival benefit in germline BRCA carriers, and CDK inhibitors such as abemaciclib have shown efficacy in reducing recurrence in ER+, HER2-negative breast cancer. We will explore the biologic underpinnings of endocrine resistance in germline BRCA mutation carriers, review existing data from retrospective studies and subgroup analyses of major trials as well as discuss implications for clinical practice. We will also highlight emerging therapeutic strategies and identify areas for future research which would be aimed at overcoming resistance and improving outcomes for this unique patient population."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA2 • ER • HER-2

Abemaciclib in Combination with Hormonal Therapy for Chemotherapy-Treated Patients With ER+/HER2- Metastatic Breast Cancer (GBCC 2025) - "Median PFS of patients with prior treatment history with CDK4/6 inhibitor (palbociclib) (n = 59) was 6.6 months (95%CI: 4.8-8.5). Abemaciclib, in combination with endocrine therapy, demonstrated considerable efficacy and manageable safety profiles in chemotherapy-treated HR+/HER2- MBC patients. Notably, the extended PFS of over one year, when abemaciclib is used as maintenance therapy after chemotherapy due to reasons other than disease progression, underscores its potential utility."

Clinical • Combination therapy • Metastases • Anorexia • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Interstitial Lung Disease • Musculoskeletal Pain • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ER • HER-2

First CDK4/6 Inhibitor for HR+/HER2- EBC: Abemaciclib-Increasing the Chance for Cure (GBCC 2025) - "The results from the monarchE studies highlight the role of abemaciclib as an advancement in the treatment of HR+/HER2- breast cancer. By significantly extending survival and reducing recurrence in patients with high- risk EBC, abemaciclib has established itself as a key component in the fight against breast cancer."

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

ET-Based Combinations and Novel Agents in HR+/HER2- Advanced Breast Cancer (GBCC 2025) - "Tumors with alterations in the PIK3CA/AKT/PTEN pathway may be offered a pathway inhibitor such as capivasertib or alpelisib, and patients with high risk recurrence of HR+ disease with a PIK3CA mutation may benefit from early introduction of a first-line inavolisib triplet...The oral SERD elacestrant is approved as monotherapy in pretreated patients with tumors harboring an ESR1 mutation. Additional oral SERDs, including imlunestrant, camizestrant, and giredestrant, have demonstrated activity and are in registrational trials. An additional maneuver in the pretreated space includes continuation of a CDK4/6 inhibitor after prior CDK4/6 inhibitor, with activity seen from switching to abemaciclib or ribociclib from a prior agent, and novel CDK inhibitors are in trials as a next generation approach. The mTOR inhibitor everolimus remains an option for pretreated patients as well, particularly when actionable mutations are not present. The continued introduction of novel agents..."

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

Screening or Early Detection of Brain Metastases and the Treatment in the Era of New Agents (GBCC 2025) - "Advances in systemic therapy have been greatest in HER2-positive breast cancer, where the current NCCN guidelines include a growing list of CNS-active regimens, such as tucatinib-capecitabine-trastuzumab, T-DXd, T-DM1, high dose trastuzumab and pertuzumab, neratinib-capecitabine, and lapatinib-capecitabine...There are a number of novel blood-brain-barrier (BBB) penetrant HER2-targeted tyrosine kinase inhibitors (e.g. ZN1041, IAM1363) in early-phase clinical trials. For patients with HER2-negative tumors, the data are more sparse; however, activity of chemotherapy drugs such as capecitabine, anthracyclines, platinums, and eribulin has been reported...Ongoing clinical trials are testing a wide variety of ADCs, such as patritumab deruxtecan, datopotamab deruxtecan, ARX788, and others...For example, the ELECTRA trial is testing the combination of elacestrant and abemaciclib. Overall, the expanding array of systemic options with clinically meaningful intracranial activity, as..."

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

Discovery of 14-3-3 Proteins YWHAB/YWHAZ as Regulators of CDK4/6 Inhibitor Resistance (GBCC 2025) - "The standard treatment for metastatic and high-risk early HR+ breast cancer includes CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) with endocrine therapy, significantly improving survival with a well-tolerated profile. Our study unveils a previously undescribed mechanism that regulates CDK4/6 inhibitor resistance and suggests the potential of further investigation of 14-3-3 proteins, especially YWHAB and YWHAZ, in breast cancer research."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AURKA • CDK2 • HER-2 • YWHAZ

PIKASSO-01: A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=193 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: May 2025 ➔ Dec 2025

Monotherapy • Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread (clinicaltrials.gov) - P1 | N=198 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • CDK6 • HER-2

Impact of Patient Profile on CDK4/6 Inhibitor Therapy Outcomes: A Real-World Data Analysis. (PubMed, Int J Mol Sci) - "We conducted a retrospective cohort study analyzing the outcomes of 95 patients with metastatic ER-positive, HER2-negative breast cancer (BC) treated with CDK4/6 inhibitors (ribociclib, palbociclib, and abemaciclib) in combination with endocrine therapy. This study highlights the significance of personalized treatment strategies based on patient age, comorbidities, and tumor biology. Ribociclib shows superior efficacy in younger, less comorbid patients, while palbociclib remains a viable option for older patients with higher comorbidity burdens."

Journal • Real-world evidence • 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 • ER • HER-2

Combination therapy of cell cycle inhibitor and HDAC inhibitor induces metabolic alterations in pancreatic cancer (AACR 2025) - "Our initial results show that combination therapy of a cell cycle inhibitor Abemaciclib (Abe), and histone deacetylase inhibitor Panobinostat (Pan) effectively decreases pancreatic cancer cell proliferation and growth and causes apoptotic cell death. These results suggest that mitochondrial dysfunction may underlie the Abe and Pan combination treatment, impairing metabolic homeostasis and energy balance. Our future studies include deciphering the in-depth mechanism of alterations in mitochondrial dynamics and metabolic signaling pathways upon combining cell cycle and HDAC inhibitor treatment in pancreatic cancer cells by performing transcriptomic profiling on PDAC cells and in vivo xenograft studies."

Combination therapy • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Cardiovascular Adverse Events and Associated Costs of CDK4/6 Inhibitors in Patients With Breast Cancer. (PubMed, J Natl Compr Canc Netw) - "Palbociclib was associated with a significantly lower risk of MACE compared with ribociclib in patients with breast cancer. Patients who developed hypertension or MACE incurred substantially higher health care costs. These findings underscore the importance of minimizing CV adverse events in patients with breast cancer treated with CDK4/6 inhibitors."

Adverse events • Journal • Breast Cancer • Cardiovascular • Hypertension • Oncology • Solid Tumor

The impact of ethnicity on benefit from novel drugs approved for breast cancer treatment: a systematic review and meta-analysis of randomized phase 3 trials of the last decade. (SABCS 2024) - "23 phase III RCTs were identified in the aBC setting, with 1547 (11.1%) patients of Asian ethnicity. Experimental drugs tested included CDK4/6i (palbociclib, ribociclib, abemaciclib), SERD (elacestrant), PI3Ki (alpelisib), PARPi (olaparib, talazoparib), broad variety of anti-HER2 drugs (tucatinib, trastuzumab deruxtecan, pertuzumab, T-DM1, neratinib, margetuximab), anti-PD-1 and anti-PD-L1 drugs (pembrolizumab, atezolizumab) and anti-TROP2 drug (sacituzumab govitecan). 16 RCTs provided HR (95%CI) for PFS in the subgroup of Asians and 17 RCTs for Non-Asians."

IO biomarker • P3 data • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Disproportionality analysis of interstitial lung disease associated with novel antineoplastic agents during breast cancer treatment: a pharmacovigilance study. (PubMed, EClinicalMedicine) - "We identified 9 agents with reporting signals for ILD in FAERS: ROR and 95% confidence interval (CI) for trastuzumab deruxtecan was 12.17 (95% CI 11.04-13.41), atezolizumab 6.04 (5.02-7.28), everolimus 3.21 (2.95-3.50), abemaciclib 2.87 (2.52-3.27), pertuzumab 2.84 (2.49-3.25), olaparib 2.29 (1.65-3.19), trastuzumab emtansine 2.27 (1.91-2.69), pembrolizumab 2.06 (1.65-2.58), and trastuzumab 1.36 (1.25-1.49). These findings highlight the need for vigilant ILD monitoring but require validation through prospective studies to clarify true clinical risks. None."

Adverse events • Journal • Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

In Vitro Drug Profiling to Guide Treatment for Relapse/Refractory AML (ASH 2024) - "Significant correlation was observed among drugs of the same classes, for example between inhibitors of PARP (e.g. niraparib-talazoparib, r=0.78, p=1.3e-22), proteasome (e.g. bortezomib-ixazomib, r=0.90, p=4.2e-36), JAK (ruxolitinib-tofacitinib, r=0.91, p=8.3e-35), MEK (cobimetinib-trametinib, p=0.93, p=8.8e-47) and CDK (abemaciclib-palbociclib, p=0.56, p=2.7e-10), confirming that the readout is biologically meaningful. Intriguingly, there were unexpected correlations between specific pairs of drugs of different classes, for instance homoharringtonine (protein translation inhibitor)-abemaciclib (CDK inhibitor) (r=0.65, p=4.3e-17) and between specific gene mutations and drug sensitivity was observed, e.g. sensitivity of CEBPAbZIP mutated samples to PARP inhibitors (p=0.00156), and of AML with inv(16) to MEK inhibitors (p=0.0016)...Drug response to daunorubicin showed good prediction of chemo-resistance in patients who had non-remission after "7+3" (ROC curve AUC..."

Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • ANXA5 • FLT3

Cryogenic volume electron microscopy reveals restoration of organelle integrity by abemaciclib in hormone receptor-positive, HER2-negative metastatic breast cancer organoids (AACR 2025) - "Abstract is embargoed at this time."

Late-breaking abstract • 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 • HER-2

The use of human small intestinal organoids as a preclinical screening tool to assess gastrointestinal toxicity induced by CDK inhibition (AACR 2025) - "All intestinal lineages were present in the organoids and resembled the frequency of linage observed in vivo.The effect of several clinically available CDKIs, such as Dinaciclib, Palbociclib and Abemaciclib, some of them known to induce GI toxicity were assessed. Whereas Palbociclib was the least toxic compound within the human organoid assay, reflecting clinical data that shows the lowest incidence of severe diarrhea.We conclude that organoids are a predictive preclinical model that can be used to identify potential on-target, off-tissue GI toxicities induced by novel therapeutics such as CDKIs. Toxicity and mechanism of action (MOA) can all be addressed in vitro to potentially reduce in vivo experimentation."

Preclinical • Hematological Malignancies • Oncology

Simultaneous targeting of CDK4/6 and BETs is independent of RB status in osteosarcoma (AACR 2025) - "In comparison to wildtype (WT) clones, KO clones were 2-10-fold more resistant to palbociclib and at most 2-fold more resistant to abemaciclib; with differences attributed to broader selectivity profile of abemaciclib...Additionally, RB monoallelic OS PDX models TT2 (pretreated) and PDX96 (naïve), were treated for 6 weeks with CDK4/6i (palbociclib, 40mg/kg, BETi (AZD5153,1 mg/kg), or their combination and significantly reduced tumor growth compared to single agents in both models (p<0.05) and was well tolerated...Future studies will extend dosing duration and focus on metastatic and RB- variant models. These findings provide rationale for further study of novel therapeutic options which may expand the clinical utility of CDK4/6i regardless of RB status."

Eye Cancer • Oncology • Osteosarcoma • Retinoblastoma • Sarcoma • Solid Tumor • ANXA5 • CDK4 • PARP1

Phase 2 study of letrozole, abemaciclib and metformin in estrogen receptor positive recurrent endometrial cancer [WITHDRAWN] (AACR 2025) - "Addition of metformin (at plasma concentrations sufficient to inhibit the PI3K pathway) to letrozole/abemaciclib is feasible and safe, and appears to induce deeper responses (including complete responses) and more prolonged PFS than letrozole/abemaciclib alone. NSMP tumors without RB1 and CCNE1 alterations derive the most benefit from this regimen."

P2 data • Endometrial Cancer • Oncology • Solid Tumor • AMPK • CCNE1 • ER • IGF1 • PGR • POLE • RB1 • TP53

Cryobiopsy for diagnosing acute fibrinous and organizing pneumonia during breast cancer treatment: A case report. (PubMed, Exp Ther Med) - "The present report describes a case of acute fibrinous and organizing pneumonia (AFOP) in a 52-year-old female patient undergoing adjuvant therapy with abemaciclib following breast cancer surgery...Following two 3-day doses of 1 g intravenous methylprednisolone therapy, tacrolimus (2 mg/day) was administered and the patient was switched to oral prednisolone. The patient was discharged on the 25th day of hospitalization. Advances in bronchoscopic techniques, including TBLC, may aid in diagnosing lung injuries."

Journal • Breast Cancer • Infectious Disease • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Pre-operative abemaciclib in localized cisplatin-ineligible MIBC with tissue and ctDNA molecular response validation (CLONEVO) (AACR 2025) - "Abstract is embargoed at this time."

Circulating tumor DNA • Bladder Cancer • Oncology

Targeting the LINC00355-MENIN interaction with CDK4/6 inhibitors to reduce proliferation in late relapse breast cancer (AACR 2025) - "To investigate this, we treated the ER+ primary breast cancer cell line MCF7 (wild-type) and the long-term estrogen-deprived (LTED) cell line - mimicking late relapse with CDK4/6 inhibitors, including Abemaciclib, Palbociclib, and Ribociclib. However, combination treatment with LINC00355 LNA ASOs and Palbociclib or Ribociclib resulted in a notable reduction in cell proliferation. These findings highlight the critical role of lncRNA-protein interactions, such as LINC00355-MENIN, in promoting cellular proliferation and provide proof-of-concept for targeting lncRNAs that can cause resistance to CDK4/6 inhibitors for late relapse breast cancer."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDKN1B • ER • HER-2