fulvestrant / Generic mfg. - 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

Endocrine-based strategies after CDK4/6 inhibitors in biomarker-selected subgroup of hormone receptor positive advanced breast cancer: A systematic review and network meta-analysis. (PubMed, Cancer Treat Rev) - "This meta-analysis reinforces the importance of molecular stratification in treatment decisions after CDK4/6i progression, highlighting the need for efficacy and safety assessments across biomarker-selected subgroups."

Biomarker • Journal • Retrospective data • Review • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • ER • PI3K • PTEN

17 β-Estradiol Inhibits GSDME-Mediated Pyroptosis in ERα-Positive Breast Cancer Cells by Promoting GSDME Promoter Methylation. (PubMed, J Steroid Biochem Mol Biol) - "To test this hypothesis, we treated MCF-7 and T47D ER-positive breast cancer cells with 17-β-estradiol (E2), either alone or in combination with selective ERα antagonist AZD9496, selective ERβ antagonist PHTPP, DNA methyltransferase (DNMT) inhibitor RG108, and selective ER degrader Fulvestrant (Ful). RG108 strengthened UV-C-induced pyroptosis, and Ful reversed the inhibitory effects of E2 on UV-C-induced pyroptosis of MCF-7 and T47D cells. Taken together, our study suggests that E2 down-regulated GSDME expression in ERα-positive breast cancer by promoting GSDME promoter methylation, and inhibited UV-C-induced pyroptosis."

Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ANXA5 • DNMT1 • ER • GSDME

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 Selective Estrogen Receptor Degrader ZN-c5 Has Broad Anti-Tumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models. (PubMed, Mol Cancer Ther) - "Fulvestrant, a selective estrogen receptor degrader (SERD) that antagonizes and degrades ER simultaneously, has demonstrated activity in ER+/HER2- breast cancers the ability to overcome endocrine resistance. These data support the clinical utility of ZN-c5 as monotherapy and as a combination therapy for patients with ER+/HER2- breast cancers. While encouraging plasma exposure and tolerability have been observed for ZN-c5 in patients, further studies are needed to optimize its therapeutic efficacy."

Journal • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Rheumatology • Solid Tumor • ER • HER-2

Pharmacokinetics (PK), safety, and tolerability of lasofoxifene in healthy Chinese female adults: results from an open-label, single-dose phase I study (ESMO Asia 2025) - P | "LAS monotherapy was more effective than fulvestrant monotherapy at inhibiting tumour growth in mice bearing human breast carcinoma xenografts harbouring activating estrogen receptor 1 mutations, and so was LAS plus palbociclib versus fulvestrant plus palbociclib. There was no marked difference in drug exposure between premenopausal and postmenopausal healthy Chinese female adults following one dose of oral LAS 5 mg. No clinically relevant differences in PK of LAS were observed for the Chinese healthy females in this study when compared cross-trial to data from Japanese and Caucasian healthy females. LAS was safe and well tolerated."

Clinical • P1 data • PK/PD data • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Efficacy of ribociclib plus fulvestrant in patients with hormone receptor-positive, HER2-negative recurrent or metastatic breast cancer at Vietnam National Cancer Hospital (ESMO Asia 2025) - "Treatment with Ribociclib in combination with Fulvestrant in patients with hormone receptor-positive and HER2-negative recurrent or metastatic breast cancer is a safe and effective regimen, especially in first-line therapy. This regimen should be widely used in clinical practice."

Clinical • 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

Efficacy of fluvestrant with cyclic dependent kinase 4/6 inhibitors when used first- versus second-line in advanced breast cancer: A patient level meta-analysis (ESMO Asia 2025) - "In HR+/HER2– advanced breast cancer, combining fulvestrant with CDK4/6 inhibitors as second-line therapy improves both PFS and OS. In contrast, when used as first-line therapy, CDK4/6 inhibitors offer a PFS benefit but no significant improvement in OS."

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

AKT inhibitors for advanced metastatic breast cancer: Meta-analysis of their efficacy and safety across hormone receptor (HR) and HER2 status-based subtypes (ESMO Asia 2025) - "Background: Trials combining novel AKT inhibitors, Capivasertib and Ipatasertib, within the standard therapy (SoC) of breast cancer have reported variable results across its subtypes. AKT inhibitors demonstrated favourable clinical response in the HR+/HER2- subtype when combined with endocrine therapy (fulvestrant), as well as in PI3K/AKT-altered subgroups within both HR+ and TNBC subtypes. Future trials should prioritize the enrolment of participants with PI3K/AKT alterations or other targetable molecular vulnerabilities to better assess their therapeutic potential."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • 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

Results of repeat core needle biopsies in ER+/HER2-negative breast cancer following neoadjuvant endocrine therapy with fulvestrant+triptorelin+ribociclib in premenopausal women (ESMO Asia 2025) - "The fulvestrant+triptorelin+ribociclib combination (NET) induced rapid reduction in proliferative activity (Ki-67), modulation of hormone receptor expression. Observed changes may reflect the tumor heterogeneity or pharmacodynamic treatment effects. The clinical significance of marker dynamics requires long-term follow-up to assess prognostic value."

Biopsy • Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

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

Phase I study of fulvestrant in combination with 177Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. (ASCO-GI 2026) - P1 | "Funded by University of Chicago Internal Cancer Center Funding Clinical Trial Registration Number: NCT06663072 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Combination therapy • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

ERADICATE: A phase Ib/II study of elacestrant plus trastuzumab deruxtecan in patients with CDK4/6 inhibitor and endocrine-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer (SABCS 2025) - "We recently generated preclinical data showing that the SERD fulvestrant produces synergistic activity with the chemotherapeutic agents fluorouracil and capecitabine in ESR1-mutant HR+ breast cancer cell lines.1 We also showed that in ER+/HER2- tumors, higher HER2 expression is associated with higher ER signaling.2 The phase Ib/II ERADICATE trial will evaluate the safety and efficacy of elacestrant plus T-DXd in patients with endocrine-resistant, HER2-low or HER2-ultralow HR+/HER2- MBC. Eligible patients include women or men age ≥ 18 years with HR+/HER2-low or HER2-ultralow (by local pathology review) unresectable locally advanced or metastatic breast cancer. Serial research blood samples will be collected for circulating tumor DNA (ctDNA) analyses. ERADICATE is currently pending the start of accrual."

Clinical • Metastases • P1/2 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 • PGR

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

Capivasertib plus fulvestrant in hormone receptor-positive (HR+) advanced breast cancer (ABC): exploratory ctDNA analyses from the Phase 3 CAPItello-291 trial (SABCS 2025) - "ctDNA analysis offers a minimally invasive option to identify PIK3CA/AKT1/PTEN alterations in HR+ ABC, particularly for pts without suitable tumor tissue analysis. However, ctDNA testing alone may miss alterations, such as in cases of low ctDNA shedding (TF <0.1%), warranting a confirmatory tissue test. The PFS benefit of C + F vs pbo + F in the ctDNA-altered group was consistent with the primary tissue-based analysis."

Circulating tumor DNA • Metastases • P3 data • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • CDK4 • HER-2 • PIK3CA • PTEN

Real-world outcomes of trastuzumab deruxtecan with or without endocrine therapy in her2-low, hormone receptor-positive metastatic breast cancer: a propensity-matched analysis (SABCS 2025) - P1 | "Real-World Outcomes of Trastuzumab Deruxtecan with or without Endocrine Therapy in HER2-Low, Hormone Receptor-Positive Metastatic Breast Cancer: A Propensity-Matched AnalysisAuthors (max 50): 21Michela Palleschia, Alberto Farolfia, Caterina Giannia, Giulia Miserocchia, Matilde Corianòb, Nicola Gentilic, Marita Mariottia, Giandomenico Di Mennaa, Olga Serraa, Chiara Casadeia, Francesca Rusconid, Alice Andalòc, Simone Sabbionia, Andrea Carlinia, Daniela Montanaria, Marianna Siricoa, Roberta Maltonia, Lorenzo Cecconettoa, Samanta Sartia, Filippo Merlonia , Antonino MusolinoaAffiliation:a Medical Oncology, Breast & GYN Unit IRCCS Istituto Romagnolo per lo Studio Dei Tumori (IRST) "Dino Amadori"b Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy.c Data Unit, IRCCS Istituto Romagnolo per lo studio dei Tumori (IRST) "Dino Amadori", Meldola, Italyd TriNetX, LLC, Cambridge, MA, USA Background:Combination therapy..."

Clinical • Metastases • 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

Clinical and genomic biomarkers of capivasertib response in patients with hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2- MBC) (SABCS 2025) - "In this study of patients with HR+/HER2- MBC treated with capivasertib and fulvestrant, alterations in CCND1 and ARID1A in ctDNA were associated with poorer PFS, while ESR1 and PI3K pathway co-mutations trended toward worse outcomes. Patients treated in the second-line or earlier, and those without prior PI3Ki exposure, may derive greater benefit. These findings are exploratory and warrant validation but suggest specific biomarkers that may correlate with risk for early progression on an AKT inhibitor."

Biomarker • Clinical • 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 • AKT1 • ARID1A • CCND1 • ER • FGFR1 • HER-2 • PIK3CA • PTEN

Capitrue, capicorn, and capitana: three phase iiib studies to evaluate the use of capivasertib in combination with fulvestrant in patients with advanced breast cancer who have relapsed/progressed on endocrine therapy and cdk4/6 inhibitors reflecting real-world clinical practice in china, germany, belgium, portugal and spain. (SABCS 2025) - P3 | "This will enable the adaptation of CAPItello‑291 findings to diverse clinical practices and contribute to the development of globally and locally relevant oncology strategies. A joint analysis of the data gathered from the three studies is planned."

Clinical • Combination therapy • Metastases • P3 data • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • PTEN

A prospective, direct-to-patient study to evaluate clinical and molecular mechanisms of resistance to capivasertib in estrogen receptor-positive metastatic breast cancer (SABCS 2025) - "PI3Kα inhibitors including alpelisib and inavolisib improve progression free survival (PFS) in PIK3CA-mutated ER+ MBC, but are often associated with high-grade toxicities such as hyperglycemia...In the CAPItello-291 trial, capivasertib combined with fulvestrant more than doubled PFS to 7.3 months versus 3.1 months with fulvestrant alone, and exhibited a favorable toxicity profile...Since January 2025, 10 patients have been enrolled and provided pre-treatment ctDNA samples. Further study details are available at https://contributeher.wixsite.com/capivaresistance."

Clinical • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • PIK3CA • PTEN

The significance of HER2 Low status on clinical outcomes of breast cancer patients with metastatic hormone-receptor positive tumors treated in the CDK4/6 inhibitor era (SABCS 2025) - "We describe the characteristics and clinical outcomes of patients with hormone-receptor positive (HR+) metastatic BC (mBC) with HER2-low and HER2 IHC 0 tumors, treated with CDK4/6 inhibitors (CDK4/6i) prior to inclusion of trastuzumab-deruxtecan in the national formulary, in a 2.8-million-member Health Maintenance Organization (HMO)... A total of 1,067 patients were identified with a median age of 63 years, 60.7% were HER2-low, 31.4% were HER2 IHC 0 and 7.9% with missing data A total of 705 patients received first-line CDK4/6i with an aromatase inhibitor (AI) and 362 received CDK4/6i with fulvestrant (F)... This study shows that HR+/HER2- metastatic breast cancer is a mixed population of IHC scores, with 60-65% of cases being HER2-low. The limited real-world TOT duration at post-CDK4/6i progression highlights a critical unmet need for new and more efficacious treatments for patients progressing on this modern endocrine-biologic regimen. In this real-world analysis,..."

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

Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study (SABCS 2025) - " ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms...PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance... Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Table 1:Phase 2 mPFS, mo[95% CI] in all patients and subgroupsNR, not reached"

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

Phase 1/2a trial of new generation PARP1-selective inhibitor saruparib + next generation selective ER degrader (SERD) camizestrant in patients (pts) with advanced/relapsed ER+/HER2-negative or low (HER2−) breast cancer (PETRA Module 6) (SABCS 2025) - P1/2, P3 | "Pts could receive prior CDK4/6 inhibitors or fulvestrant, but not oral SERDs. Saruparib + camizestrant was well tolerated with no new safety signals versus prior monotherapy studies of each drug. PK of saruparib in combination with camizestrant was consistent with monotherapy data. Preliminary efficacy of the combination was promising and compared favorably with camizestrant monotherapy."

Clinical • Metastases • P1/2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • HER-2 • PALB2

ReDiscover-2, a phase 3 study of RLY-2608 + fulvestrant versus capivasertib + fulvestrant as treatment for locally advanced or metastatic PIK3CA-mutant HR+/ HER2- breast cancer following recurrence or progression on or after treatment with a CDK4/6 inhibitor (trial in progress) (SABCS 2025) - P3 | "While the PI3K inhibitors alpelisib and inavolisib and the AKT inhibitor capivasertib have been approved by the FDA to treat this substantial patient population, these therapies cause significant toxicity, notably hyperglycemia, rash, and diarrhea, due to their non-selective targeting of the pathway. Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication are excluded• No prior PI3K, AKT, or mTOR inhibitors or any agent whose mechanism of action is to inhibit the PI3K/AKT/mTOR pathwayReDiscover-2 (NCT06982521) is open for enrollment. For further information, contact: clinicaltrials@relaytx.com."

Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • PTEN

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 | Sponsor: 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 • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1 • PIK3CA