^
    1d
    CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen. (PubMed, NPJ Breast Cancer)
    Early clinical data demonstrated activity of BLU-222, a potent and selective CDK2 inhibitor, both as monotherapy (CCNE1 amplified) and in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. These findings provide evidence that CDK2i combined with CDK4/6i can address multiple known mechanisms of resistance to CDK4/6i, enhancing antitumor responses in preclinical breast cancer models.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1)
    |
    HR positive • HER-2 negative
    |
    Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)
    4d
    Ribociclib-Induced Hepatitis: A Case Report of Possible Autoimmune Hepatotoxicity. (PubMed, Case Rep Oncol)
    We present a case of a 59-year-old postmenopausal female with metastatic hormone receptor-positive breast cancer who started treatment with fulvestrant and ribociclib after progression on anastrozole...Ribociclib was held, and after no improvement in 28 days, she was treated with a 6-day course of prednisone 1 mg/kg, with significant improvement in her liver enzymes...Following normalization of her liver enzymes, she was rechallenged with abemaciclib with no recurrent hepatotoxicity. Ribociclib hepatotoxicity can be successfully treated with withdrawal of the medication and a short course of corticosteroids if liver enzymes do not improve following a 28-day withdrawal, highlighting a potential immune-mediated mechanism. Additionally, rechallenge with another cyclin-dependent kinase 4 and 6 inhibitor is a safe and effective strategy that should be considered.
    Journal
    |
    CDK4 (Cyclin-dependent kinase 4)
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    HR positive
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    Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • prednisone • anastrozole
    6d
    Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov)
    P1/2, N=792, Recruiting, Hoffmann-La Roche | N=580 --> 792 | Trial completion date: May 2028 --> Sep 2030 | Trial primary completion date: May 2028 --> Sep 2030
    Enrollment change • Trial completion date • Trial primary completion date
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    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PD-L1 expression • PIK3CA mutation
    |
    VENTANA PD-L1 (SP142) Assay
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • letrozole • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Actemra IV (tocilizumab) • atirmociclib (PF-07220060) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)
    6d
    Real-world outcomes with palbociclib, ribociclib, and abemaciclib plus endocrine therapy in HR+/HER2- advanced breast cancer: A multicenter retrospective study. (PubMed, Breast)
    Endocrine sensitivity/resistance and ET partner were major determinants of outcome with CDK4/6i plus ET in HR+/HER2- ABC, informing individualized treatment selection and sequencing.
    Retrospective data • Journal • Real-world evidence
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    HER-2 (Human epidermal growth factor receptor 2)
    |
    HR positive • HER-2 negative
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant
    7d
    (VELA) Study of BLU-222 in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=50, Terminated, Blueprint Medicines Corporation | Phase classification: P1/2 --> P1 | N=366 --> 50 | Trial completion date: Sep 2026 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2025 --> Jul 2025; This trial was terminated prior to the initiation of Phase 2 for reasons not due to safety concerns.
    Phase classification • Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)
    |
    HER-2 negative
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    carboplatin • Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)
    7d
    Safety evaluation of selective estrogen receptor degraders (SERDs) using real-world evidence from the FDA Adverse Event Reporting System (FAERS). (PubMed, Sci Rep)
    The analysis commenced with elacestrant (2022) and fulvestrant (2004), concluding in the fourth quarter of 2024. For fulvestrant, increased vigilance is necessary regarding cancer metastasis and adverse events impacting the hematological and lymphatic systems. It is recommended that targeted monitoring be enhanced in clinical practice in accordance with the distinct characteristics of each drug.
    Journal • Adverse events • HEOR • Real-world evidence
    |
    ER (Estrogen receptor)
    |
    fulvestrant • Orserdu (elacestrant)
    8d
    Hybrid Dihydropyrimidinones Targeting AKT Signaling: Antitumor Activity in Hormone-Dependent 2D and 3D Cancer Models. (PubMed, Pharmaceutics)
    Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. Xanthene- and pyran-based hybrids-particularly SJ028, SJ064, and SJ078-showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers.
    Preclinical • Journal
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    CASP3 (Caspase 3) • CASP7 (Caspase 7)
    |
    tamoxifen • fulvestrant • letrozole • MK-2206
    8d
    FAKTION: Fulvestrant +/- Akt Inhibition in Advanced Aromatase Inhibitor Resistant Breast Cancer (clinicaltrials.gov)
    P1/2, N=149, Active, not recruiting, Velindre NHS Trust | Phase classification: P1b/2 --> P1/2 | Trial completion date: Dec 2023 --> Dec 2025
    Phase classification • Trial completion date
    |
    fulvestrant • Truqap (capivasertib)
    8d
    SPEAR: Study of PIK3CA Mutations and Effectiveness and Tolerability Outcomes of Alpelisib in Real-world (clinicaltrials.gov)
    P=N/A, N=600, Completed, Novartis Pharmaceuticals | Recruiting --> Completed | N=200 --> 600 | Trial completion date: Sep 2025 --> Feb 2025 | Trial primary completion date: Sep 2025 --> Feb 2025
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Real-world evidence
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HR positive • HER-2 negative • PIK3CA mutation
    |
    Piqray (alpelisib) • fulvestrant
    9d
    Study for Participants Continuing From Pfizer-sponsored Palbociclib (a Study Medicine) Studies (clinicaltrials.gov)
    P2, N=35, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    Erbitux (cetuximab) • Ibrance (palbociclib) • fulvestrant • letrozole
    13d
    Health-related quality of life with first- vs second-line CDK4/6 inhibitor use in advanced breast cancer: results from the SONIA trial. (PubMed, J Natl Cancer Inst)
    HRQoL was comparable between patients receiving CDK4/6i in first- versus second-line across all measures, despite differences in toxicity rates.
    Journal • HEOR
    |
    CDK4 (Cyclin-dependent kinase 4)
    |
    fulvestrant
    13d
    HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=54, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Aug 2025 --> Dec 2025
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    PGR positive
    |
    Lynparza (olaparib) • Ibrance (palbociclib) • fulvestrant