fulvestrant

This enabled a medium-throughput drug screen to identify Selumetinib and Fulvestrant, as inhibitors of glioma invasion in vivo. Thus, the Hi-Q approach can easily be adapted to reliably harness brain organoids' application for personalized neurogenetic disease modeling and drug discovery.

P2, N=379, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> Nov 2024

P1, N=285, Completed, AstraZeneca | Active, not recruiting --> Completed

P1, N=200, Active, not recruiting, Genentech, Inc. | Trial completion date: Nov 2024 --> Dec 2026 | Trial primary completion date: Nov 2024 --> Dec 2026

Treatment distribution was as follows: 15 patients received palbociclib (38%), 19 ribociclib (49%), and five abemaciclib (13%). Most patients received fulvestrant (31 patients, 79%), whereas eight patients (21%) were treated with letrozole...FDG-PET-CT performed before cyclin-dependent kinase 4/6 inhibitor commencement is a valuable prognostic tool in hormone receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer. Patients with SUVmax less than 8.4 experienced extended progression-free survival compared to those with higher SUVmax.

P3, N=510, Active, not recruiting, Olema Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

P3, N=701, Recruiting, Celcuity Inc | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Sep 2024 --> Mar 2025

Abemaciclib+fulvestrant significantly improved PFS after disease progression on prior CDK4/6i+ET in patients with HR+, HER2- ABC, offering an additional targeted therapy option for these patients.

P1, N=140, Not yet recruiting, Synnovation Therapeutics, Inc.

P1/2, N=46, Terminated, Henan Cancer Hospital | Trial completion date: Jan 2026 --> Jul 2024 | Active, not recruiting --> Terminated; Investigators' decision

Baseline ESR1 mutations in EV-DNA were associated with shorter progression-free survival (PFS) across the cohort, with the Y537S mutation showing a particularly strong impact on the outcome of fulvestrant-treated patients. In contrast, PIK3CA mutations in EV-DNA did not significantly correlate with PFS, whereas in ctDNA, they were linked to poor outcomes. Altogether, this study positions EV-DNA as a valuable biomarker alongside ctDNA, enriching the understanding of different analytes in liquid biopsy and supporting strategies for HR+/HER2-mBC in precision oncology.

P=N/A, N=80, Recruiting, Hunan Cancer Hospital

P3, N=500, Recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Jun 2026 --> Apr 2028 | Trial primary completion date: Jun 2025 --> Apr 2027

Recent studies indicate that adding inavolisib, a PI3Kα inhibitor, to palbociclib/fulvestrant benefits patients with endocrine-resistant HR+/HER2- metastatic breast cancer with a PIK3CA mutation. Alpelisib and capivasertib are both US Food and Drug Administration (FDA) approved in combination with fulvestrant in patients with endocrine-resistant HR+/HER2-, PIK3CA-mutant metastatic breast cancer, both with activity in the post-CDK4/6 setting...Toxicity profiles of all agents necessitate careful patient selection. Several mutant-selective and pan-mutant-selective novel inhibitors are under investigation with the potential to improve tolerability and efficacy.

P=N/A, N=419, Completed, MedSIR | Active, not recruiting --> Completed | Trial primary completion date: Oct 2024 --> May 2024

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=200, Recruiting, Oana Danciu | Trial completion date: Dec 2027 --> Aug 2029 | Trial primary completion date: Dec 2024 --> Aug 2028

We report a case of a 61-year-old female with HR+HER2- metastatic breast cancer (MBC) who developed resistance to fulvestrant and subsequent chemotherapy but achieved a durable partial response (PR) lasting more than 22.5 months following ESG401 treatment. Furthermore, the patient's exceptionally long clinical benefit distinguishes her from other patients receiving ESG401 treatment. Further exploration of the use of ESG401 in HR+HER2- MBC patients, as well as a deeper understanding of the characteristics of patients that may impact sustained efficacy, in expanded clinical trials is warranted.

P2, N=31, Recruiting, Sarah K. Lynam MD | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=24, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P1/2 --> P1 | Trial completion date: Mar 2025 --> Jul 2025

P1/2, N=280, Not yet recruiting, Novartis Pharmaceuticals

While anti-estrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations...Combining imlunestrant with abemaciclib (CDK4/6 inhibitor), alpelisib (PI3K inhibitor), or everolimus (mTOR inhibitor) further enhanced tumor growth inhibition, regardless of ESR1 mutational status. In an ER+ breast cancer intracranial tumor model, imlunestrant prolonged survival compared to vehicle or alternative SERD therapies. Together, these finding support the potential of imlunestrant to degrade ERα and suppress the growth of ESR1 wildtype and mutant breast cancer, including brain metastatic tumors.

P3, N=463, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2024 --> Jan 2026

P2, N=169, Completed, Melissa K Accordino | Active, not recruiting --> Completed

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, N=168, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed

P3, N=460, Recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd. | Initiation date: Feb 2025 --> Nov 2024

Hormonal or endocrine therapy includes selective estrogen receptor modulators (SERMs) such as raloxifene, tamoxifen and toremifene, selective estrogen-receptor degraders (SERDs) including elacestrant and fulvestrant, and aromatase inhibitors such as anastrozole, letrozole, and exemestane...These agents include taxanes (docetaxel, nab-paclitaxel, and paclitaxel), anthracyclines (doxorubicin, epirubicin), anti-metabolites (capecitabine, gemcitabine, fluorouracil, methotrexate), alkylating agents (carboplatin, cisplatin, and cyclophosphamide), and drugs that target microtubules (eribulin, ixabepilone, ado-trastuzumab emtansine). Patients with ER-positive tumors are treated with 5-10 years of endocrine therapy and chemotherapy. For patients with metastatic breast cancer, standard first-line and follow-up therapy options include targeted approaches such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PDL1 immunotherapy, depending on the tumor type and molecular profile.

At its current price, our analysis suggests that the addition of capivasertib to fulvestrant as a second line treatment is not cost effective versus fulvestrant alone at a willingness-to-pay threshold of $100,000/QALY. The price of capivasertib will need to be reduced by nearly 70% (to $7000 per cycle) for it to become cost effective.

These findings highlight the ongoing difficulties in demonstrating clear clinical utility of CGP tests in Japan, emphasizing the need for broad discussions on its future direction.

These results suggest that the suppression of FOXO3a and ERα led to the increased expression of TGF-α, EGFR, and HER2 and subsequent cell proliferation in Ful-R. This study highlights the potential development of therapeutic drugs targeting FOXO3a for the treatment of HER2-positive, estrogen, and progesterone receptor-negative her2-type proliferative breast cancers.

P1, N=72, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Dec 2024 --> Mar 2026 | Trial primary completion date: Dec 2024 --> Mar 2026

Further, IGFBP-3 expression was increased by treatment with the GPER1 agonist G-1 and attenuated upon treatment with P17, a YAP/TAZ inhibitor. These data suggest that IGFBP-3 modulates breast cancer cells and is a mediator of breast cancer cell response to fulvestrant and tamoxifen.

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.

P2, N=333, Completed, Queen Mary University of London | Unknown status --> Completed

P3, N=230, Recruiting, Hoffmann-La Roche | Trial completion date: Oct 2028 --> Jan 2028 | Trial primary completion date: Oct 2028 --> Oct 2026

P3, N=460, Recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

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.

P2, N=69, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Aug 2025 --> Feb 2025

P2, N=33, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

P1, N=138, Recruiting, BeiGene | Trial completion date: Dec 2026 --> Feb 2028 | Trial primary completion date: Dec 2026 --> Feb 2028

P3, N=624, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting