^
1d
Fasting-mimicking diet potentiates anti-tumor effects of CDK4/6 inhibitors against breast cancer by suppressing NRAS- and IGF1-mediated mTORC1 signaling. (PubMed, Drug Resist Updat)
These findings expand the mechanistic understanding of the FMD-mediated increase in drug efficacy and provide further evidence to support trials combining hormone therapy, CDK4/6 inhibitors, and FMD in breast cancer treatment. These new results on FMD cycles add an optimistic outlook to extend the efficacy of standard-of-care drugs that eventually become ineffective because of acquired resistance.
Journal
|
NRAS (Neuroblastoma RAS viral oncogene homolog) • IGF1 (Insulin-like growth factor 1)
2d
Continuation of CDK4/6 Inhibition and Switching of Hormonal Therapy After Progression on Prior CDK4/6 Inhibitors in HR+/HER2- Breast Cancer: A Systematic Review and Meta-Analysis. (PubMed, Cureus)
The PFS benefit was more pronounced in those individuals who received abemaciclib or ribociclib as second CDK4/6i. Continuation of CDK4/6 inhibition was associated with higher rates of grade 3 and 4 neutropenia (range: 25-40%) and anemia (range: 1.7-11%). In conclusion, switching CDK4/6i and ET conferred a statistically significant improvement of PFS in comparison to ET alone in patients with progression or recurrence on prior CDK4/6i-containing therapy.
Clinical • Retrospective data • Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HER-2 negative • EGFR positive
|
Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib)
2d
New trial • Combination therapy • Real-world evidence • Real-world • Metastases
|
Keytruda (pembrolizumab) • Focus V (anlotinib) • Tyvyt (sintilimab) • capecitabine • albumin-bound paclitaxel • fulvestrant • etoposide IV • Halaven (eribulin mesylate)
2d
OMERIC: Omic Technologies to Track Resistance to Palbociclib in Metastatic Breast Cancer (clinicaltrials.gov)
P=N/A, N=25, Active, not recruiting, Centre Oscar Lambret | Recruiting --> Active, not recruiting | Trial completion date: Sep 2023 --> Sep 2025 | Trial primary completion date: Sep 2023 --> Sep 2025
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 negative
|
Ibrance (palbociclib)
3d
Designing a Time-Dependent Therapeutic Strategy using CDK4/6 Inhibitors in an Intracranial ATRT Model. (PubMed, Neuro Oncol)
Metronomic IT delivery of palbociclib enhances drug efficacy and safety, improves survival, and offers a promising treatment strategy for PBTs with CSF dissemination.
Journal
|
PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CCNA2 (Cyclin A2) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1) • GFAP (Glial Fibrillary Acidic Protein)
|
Ibrance (palbociclib)
5d
Spherical Manifolds Capture Drug-Induced Changes in Tumor Cell Cycle Behavior. (PubMed, Pac Symp Biocomput)
CDK4/6 inhibitors such as palbociclib block cell cycle progression and improve outcomes for many ER+/HER2- breast cancer patients...Understanding the molecular mechanisms that allow treated tumor cells to evade arrest is critical for identifying targets of future therapies. Ultimately, we seek to further SPCA as a tool of precision medicine, targeting treatments by individual tumors, and extending this computational framework to interpret other cyclical biological processes represented by high-dimensional data.
Journal • Tumor cell
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCND1 (Cyclin D1) • CDK2 (Cyclin-dependent kinase 2)
|
HER-2 negative • CCND1 expression • CDK2 expression
|
Ibrance (palbociclib)
5d
Study to Evaluate the Extended Overall Survival (OS) Data From PARSIFAL Study (The PARSIFAL-LONG Study) (clinicaltrials.gov)
P=N/A, N=419, Completed, MedSIR | Active, not recruiting --> Completed | Trial primary completion date: Oct 2024 --> May 2024
Trial completion • Trial primary completion date • Combination therapy • Metastases
|
Ibrance (palbociclib) • fulvestrant • letrozole
5d
Palbociclib With Fulvestrant for Metastatic Breast Cancer After Treatment With Palbociclib and an Aromatase Inhibitor (clinicaltrials.gov)
P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Dec 2024 --> Jun 2025
Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PI3K (Phosphoinositide 3-kinases)
|
ER positive • HER-2 negative • ER positive + PGR positive • HER-2 negative + AR positive + ER positive • HER-2 negative + ER positive • HER-2 negative + PGR positive
|
Ibrance (palbociclib) • fulvestrant
5d
RaPhLRR: Ribociclib And Endocrine Treatment of Physician's Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (clinicaltrials.gov)
P2, N=200, Recruiting, Oana Danciu | Trial completion date: Dec 2027 --> Aug 2029 | Trial primary completion date: Dec 2024 --> Aug 2028
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
ER positive • HER-2 negative • PGR positive • HER-2 negative + AR positive + ER positive • HER-2 negative + ER positive • HER-2 negative + PGR positive
|
tamoxifen • Kisqali (ribociclib) • fulvestrant • letrozole • anastrozole • exemestane
6d
Downregulation of the splicing regulator NSRP1 confers resistance to CDK4/6 inhibitors via activation of interferon signaling in breast cancer. (PubMed, J Biol Chem)
Knockdown of NSRP1 reduces CDK4/6i (palbociclib) sensitivity of MCF7 cells while overexpression of NSRP1 sensitizes MCF7-PalR cells towards palbociclib treatment...In addition, including NSD2 exon 2 elevates NSD2 protein expression to activate the IFN signaling pathway. This study unveils the critical role of NSRP1 in regulating the IFN signaling pathway and the CDK4/6i resistance, which could be a promising biomarker for predicting therapy response.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
Ibrance (palbociclib)
6d
Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer (clinicaltrials.gov)
P1, N=42, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025
Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset) • CASP3 (Caspase 3)
|
HRD
|
Lynparza (olaparib) • Verzenio (abemaciclib)
7d
Alternative palbociclib dosing schedules for hormone receptor-positive and HER2-negative metastatic breast cancer. (PubMed, Oncology)
Dosing schedules other than the standard 3/1 schedule can be used to continue palbociclib with HR+/HER2-MBC while ensuring therapeutic efficacy. Alternative dosing schedules look promising and need further research (preferably, prospective studies) with a larger sample size and longer follow-up to validate treatment efficacy.
Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HER-2 negative • HR positive + HER-2 negative
|
Ibrance (palbociclib)
7d
Imlunestrant with or without Abemaciclib in Advanced Breast Cancer. (PubMed, N Engl J Med)
Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.).
Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
ER positive • HER-2 negative • ER mutation • EGFR positive • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
|
Verzenio (abemaciclib) • imlunestrant (LY3484356)
7d
Neoadjuvant Camrelizumab With Palbociclib for Resectable Esophageal Squamous Cell Carcinomas (clinicaltrials.gov)
P1, N=6, Recruiting, West China Hospital | Initiation date: Dec 2024 --> Aug 2024
Trial initiation date
|
Ibrance (palbociclib) • AiRuiKa (camrelizumab)
7d
ABBICAR: Bicalutamide and Abemaciclib in Inoperable or Metastatic Androgen Receptor-positive Triple-negative Breast Cancer (clinicaltrials.gov)
P2, N=53, Recruiting, Universitaire Ziekenhuizen KU Leuven | Trial completion date: Dec 2027 --> Dec 2028
Trial completion date • Combination therapy • Metastases
|
Verzenio (abemaciclib) • bicalutamide
8d
Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial. (PubMed, Gynecol Oncol)
These results support a potential role of the palbociclib-letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned.
P2 data • Journal • Metastases
|
ER (Estrogen receptor) • CCNA2 (Cyclin A2)
|
ER positive • HR positive
|
Ibrance (palbociclib) • letrozole • megestrol
8d
Testing the Addition of Copanlisib to Usual Treatment (Fulvestrant and Abemaciclib) in Metastatic Breast Cancer (clinicaltrials.gov)
P1, N=24, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P1/2 --> P1 | Trial completion date: Mar 2025 --> Jul 2025
Phase classification • Trial completion date • Combination therapy • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog)
|
HER-2 amplification • HER-2 negative • PGR positive • HER-2 negative + PGR positive
|
Prosigna™ Breast Cancer Prognostic Gene Signature Assay
|
Verzenio (abemaciclib) • fulvestrant • Aliqopa (copanlisib)
8d
New P1/2 trial • Combination therapy • Metastases
|
Kisqali (ribociclib) • fulvestrant
9d
ADELA: Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i. (clinicaltrials.gov)
P3, N=240, Recruiting, MedSIR | Not yet recruiting --> Recruiting | Initiation date: Sep 2024 --> Dec 2024
Enrollment open • Trial initiation date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
|
HER-2 mutation • ER mutation
|
everolimus • dexamethasone • Orserdu (elacestrant)
9d
Evaluation of cyclin-dependent kinase 4/6 inhibitor-induced serum creatinine elevations in patients with hormone receptor positive breast cancer. (PubMed, J Oncol Pharm Pract)
Pseudo-Scr elevation appears to be a class effect of CDK4/6i, with similar rates of Scr elevation observed across the three agents currently FDA approved.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • CDK4 (Cyclin-dependent kinase 4)
|
HR positive • HER-2 negative
|
Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib)
9d
MONARCH plus: A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer (clinicaltrials.gov)
P3, N=463, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2024 --> Jan 2026
Trial completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
HER-2 overexpression • HER-2 negative
|
Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole
11d
TRIM4 modulates the ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitor in ovarian cancer. (PubMed, Front Med)
Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616...Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Journal
|
HNRNPD (Heterogeneous Nuclear Ribonucleoprotein D) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C) • TRIM4 (Tripartite Motif Containing 4)
|
culmerciclib (TQB3616)
12d
Trial completion • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
ER positive • HER-2 negative
|
Kisqali (ribociclib) • fulvestrant
12d
Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 negative
|
Verzenio (abemaciclib)
12d
Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. (PubMed, Lancet Oncol)
BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor.
P2 data • Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
HR positive • HER-2 negative • PIK3CA mutation • PIK3CA mutation + HR positive • HR positive + HER-2 negative • HER-2 negative + HR positive + PIK3CA mutation
|
Piqray (alpelisib) • fulvestrant
12d
SARC041: Study of Abemaciclib Versus Placebo in Patients with Advanced Dedifferentiated Liposarcoma (clinicaltrials.gov)
P3, N=108, Active, not recruiting, Sarcoma Alliance for Research through Collaboration | Recruiting --> Active, not recruiting | Trial completion date: Nov 2024 --> Dec 2026 | Trial primary completion date: May 2024 --> Dec 2025
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
|
Verzenio (abemaciclib)
13d
Trial initiation date • Metastases
|
everolimus • fulvestrant • exemestane • SCR-6852
13d
First-line endocrine therapy combined with CDK 4/6 inhibitor in disseminated carcinomatosis of bone marrow (DCBM) luminal breast cancer: a case report. (PubMed, J Med Case Rep)
Notably, the combined approach of ET and CDK4/6 inhibitor represents a novel intervention in managing DCBM in patients with LBC.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
HER-2 negative
|
tamoxifen • Kisqali (ribociclib) • letrozole • leuprolide acetate for depot suspension
15d
New P2 trial
|
lobaplatin (D19466) • Cosela (trilaciclib) • Pinorubin (pirarubicin)
15d
A Phase Ib/II Study Confirmed Inhibition of Autophagy Synergizes Anti-tumor Effect of High Dose CDK4/6i (clinicaltrials.gov)
P1/2, N=29, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Trial primary completion date: Dec 2023 --> May 2024
Trial primary completion date
|
Ibrance (palbociclib) • hydroxychloroquine
16d
New P2 trial • Metastases
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • cisplatin • carboplatin • docetaxel • albumin-bound paclitaxel • Cosela (trilaciclib)
16d
Enhanced radiotherapy susceptibility in NSCLC through palbociclib-mediated PP5 inhibition. (PubMed, Biochim Biophys Acta Mol Cell Res)
Our findings provide compelling evidence that targeting PP5 can significantly enhance the therapeutic outcomes of radiotherapy in NSCLC. This research offers valuable insights into new combination therapy strategies, highlighting the potential of PP5 as a novel therapeutic target to overcome radioresistance.
Journal
|
CDK4 (Cyclin-dependent kinase 4)
|
Ibrance (palbociclib)
16d
Three sample preparation methods for clinical determination of CDK4/6 inhibitors with endocrine therapy in breast cancer patient plasma using LC-MS: Cross-validation (red), ecological (green) and economical (blue) assessment. (PubMed, J Pharm Biomed Anal)
Cyclin D-dependent kinase 4/6 inhibitors palbociclib, ribociclib and abemaciclib, in combination with aromatase inhibitors anastrozole and letrozole or oestrogen receptor degrader fulvestrant, are being assessed as candidates for therapeutic drug monitoring. DLLME proved to be the most ecologically acceptable method due to the high degree of miniaturisation (AGREEprep score 0.44), PLR enabled very high sample throughput and cost-effectiveness (BAGI 72.5), while SPE showed the best analytical performance (redness score 100). All three methods are suitable for their designated purpose, and the choice of the ideal method can be made based on the scope of application, available funds and equipment and desired ecological footprint.
Journal
|
ER (Estrogen receptor)
|
Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • letrozole • anastrozole
16d
NCI-2018-01194: Palbociclib and Sorafenib, Decitabine, or Dexamethasone in Treating Patients with Recurrent or Refractory Leukemia (clinicaltrials.gov)
P1, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=54 --> 32
Enrollment closed • Enrollment change
|
Ibrance (palbociclib) • sorafenib • decitabine
16d
Neoadjuvant Camrelizumab With Palbociclib for Resectable Esophageal Squamous Cell Carcinomas (clinicaltrials.gov)
P1, N=6, Recruiting, West China Hospital | Initiation date: Oct 2023 --> Dec 2024
Trial initiation date
|
Ibrance (palbociclib) • AiRuiKa (camrelizumab)
17d
New trial • Metastases
|
albumin-bound paclitaxel • AiRuiKang (dalpiciclib)
17d
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 negative
|
Verzenio (abemaciclib)
17d
Unveiling the Potential of Cyclin-Dependent Kinases 4 and 6 Inhibitors Beyond Progression in Hormone Receptor Positive/Human Epidermal Growth Factor Negative Advanced Breast Cancer - A Clinical Review. (PubMed, Curr Treat Options Oncol)
While some benefit, albeit modest, has been observed from switching to a different CDK4/6i after progression (e.g. ribociclib after palbociclib in the MAINTAIN trial and abemaciclib after both palbociclib and ribociclib in the postMONARCH trial), the current evidence (mainly with palbociclib) clearly argues against maintaining the same CDK4/6i. However, selected patients with indolent disease, prolonged exposure to previous CDK4/6i treatment (especially palbociclib) and without actionable molecular alterations, may be suitable for suchmaintenance strategy beyond progression. In this challenging and rapidly evolving treatment landscape, ongoing studies can refine the optimal approach and identify clinical and molecular factors to select the best treatment for the right patient.
Review • Journal • IO biomarker • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
HR positive • ER mutation
|
Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib)
18d
Characteristics, treatment patterns and survival of patients with high-risk early hormone receptor-positive breast cancer in French real-world settings: an exploratory study of the CANTO cohort. (PubMed, ESMO Open)
This real-world study confirms that patients with HR+ BC and unfavorable clinicopathological features are at risk of relapse early in their adjuvant treatment trajectory, despite (neo)adjuvant chemotherapy. It is imperative to implement innovative treatment approaches for high-risk patients, ideally adding them as early as possible to the adjuvant treatment.
Journal • Real-world evidence • Real-world
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HER-2 negative • EGFR positive
|
Verzenio (abemaciclib)
19d
Ribociclib-induced autoimmune-like hepatitis: a case report. (PubMed, J Chemother)
Initially treated for early-stage disease with surgery, chemotherapy, radiotherapy, and ET, she progressed to metastatic disease and received ribociclib, letrozole, and goserelin, achieving a partial response. Managed with prednisolone and azathioprine, ribociclib was reintroduced at a reduced dose and later escalated to full dose. This case report highlights the importance of a multidisciplinary approach to balance oncologic efficacy with hepatologic safety.
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HER-2 negative • EGFR positive
|
Kisqali (ribociclib) • letrozole • goserelin acetate
19d
Enrollment open • Metastases
|
everolimus • fulvestrant • exemestane • SCR-6852
20d
Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer. (PubMed, Nature)
All of the patients received the same endocrine therapy, consisting of an aromatase inhibitor for first-line treatment and fulvestrant for second-line treatment...First-line CDK4/6i use was associated with a longer CDK4/6i treatment duration compared with second-line use (median CDK4/6i treatment duration of 24.6 versus 8.1 months, respectively) and more grade ≥3 adverse events (2,763 versus 1,591, respectively). These data challenge the need for first-line use of a CDK4/6i in all patients.
Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HER-2 negative
|
fulvestrant