fulvestrant / Generic mfg. - LARVOL DELTA

Real-World, National Study of Palbociclib in HR+/HER2- Metastatic Breast Cancer: A 2.5-Year Follow-Up PALBO01/2021. (PubMed, Diagnostics (Basel)) - "The secondary objectives focused on treatment duration with aromatase inhibitors (AI) or fulvestrant and subsequent therapies after disease progression. PFS and OS were analyzed via the Kaplan-Meier method, with median times, 1- and 2-year estimates, and 95% confidence intervals reported. This study supports the integration of clinical trial evidence into real-world settings, enhancing patient selection and treatment personalization."

Clinical • Journal • Real-world evidence • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

UCLA B-13: Ribociclib, Tucatinib, and Trastuzumab for the Treatment of HER2 Positive Breast Cancer (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Apr 2026 ➔ Apr 2027 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Tucatinib and trastuzumab for previously treated HER2-mut MBC: Final analysis of a phase II basket study (SGNTUC-019) (ESMO-BC 2025) - P2 | "Tucatinib (TUC) is an oral tyrosine kinase inhibitor that is highly selective for HER2 and approved for previously treated HER2+ MBC with trastuzumab (Tras) and capecitabine...Pts with HR+ disease also received fulvestrant (500 mg IM Q4W starting Cycle (C) 1 Day (D) 1, and on C1D15)... With ∼10 mos of additional follow-up, TUC + Tras has demonstrated clinically meaningful efficacy with durable response to study treatment since the primary analysis and continues to show favorable tolerability in pts with previously treated HER2-mut MBC."

P2 data • Pan tumor • HER2 Positive Breast Cancer • CDK4 • HER-2

PIK3CA mutational status concordance between plasma and tumor in HER2+ advanced breast cancer (ABC) patients (pts) of ALPHABET (GEICAM/2017-01_IBCSG 62-20_BIG 18-04) trial (ESMO-BC 2025) - P3 | "We report PIK3CA mts analyses in matched baseline plasma and tumor samples in HER2+ ABC pts. ALPHABET, NCT05063786 is a randomized phase III trial comparing alpelisib + trastuzumab +/- fulvestrant vs trastuzumab + chemo...Median number of prior ABC Tx lines was 3, 32% with >3 prior anti-HER2 lines (92% pertuzumab, 96% T-DM1, 40% T-DXd, 8% tucatinib)... There was moderate agreement between plasma and tumor PIK3CA mts detection in our pts in line with what is described in luminal BC. False negatives exceeded clinical routine expected rate (5%). Our results suggest that PIK3CA mts in plasma could be a surrogate of tumor PIK3CA-mut in HER2+ ABC."

Clinical • Discordant • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • KRAS • PIK3CA • TP53

First-in-Human Study of RLY-5836 in Advanced Breast Cancer and Other Solid Tumors (clinicaltrials.gov) - P1 | N=41 | Completed | Sponsor: Relay Therapeutics, Inc. | Active, not recruiting ➔ Completed | N=265 ➔ 41

Enrollment change • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

ETX-636, a novel allosteric pan-mutant-selective PI3Kα dual inhibitor and degrader with best-in-class potential (AACR 2025) - "Orthosteric ATP-competitive inhibitors, alpelisib and inavolisib, which inhibit both Wild-type (WT) and mutant PI3Kα, are approved in combination regimens for treating PIK3CA-mutant, HR+/HER2-, advanced or metastatic BrCA...In addition to greater biochemical selectivity for mutant PI3Kα over WT PI3Kα, ETX-636 has stronger target binding affinity, better on-target potency in biochemical and cellular pharmacodynamic assays, and demonstrates superior anti-tumor activity in vivo when compared to other allosteric, pan-mutant-selective PI3Kα inhibitors (i.e. RLY-2608 and STX-478)...In an ER-positive, HER2-negative, PI3Kα-mutant BrCA xenograft, ETX-636 is efficacious as a single agent and shows synergistic activity with fulvestrant, inducing tumor regression while being well-tolerated...In addition, based on pharmacokinetic, pharmacodynamic, efficacy, and toxicology studies, predicted human efficacious doses of ETX-636 are not projected to cause hyperglycemia. The preclinical..."

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 • BRCA • ER • HER-2 • PIK3CA

INAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC). (ASCO 2025) - P2/3 | "Clinical Trial Registration Number: NCT04191499 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P3 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 • HER-2 • PIK3CA

Patient selection biomarkers for CDK7 inhibitor samuraciclib (SAM; CT7001) combined with selective estrogen receptor degrader (SERD) in hormone receptor-positive advanced breast cancer (HR+ ABC) post-CDK4/6 inhibitor (CDK4/6i) (ESMO-BC 2025) - P1/2 | "SAM was administered to patients (pts) with HR+ ABC with fulvestrant (FUL), an intramuscular (IM) SERD, or giredestrant (GIR), a highly potent, non-steroidal, PO SERD, in 2 independent studies: CT7001_001 (NCT03363893) Module 2A and MORPHEUS (NCT04802759) [Coombes et al. These independent studies suggest that patients with no evidence of either TP53 mutation or of liver metastases may preferentially benefit from SAM + SERD. The observed outcomes in this small dataset appear greater than the anticipated prognostic impact of these factors [O'Leary et al. JNCI 2021; Robertson et al."

Biomarker • Clinical • Metastases • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • CDK7 • ER • TP53

INAVO123: Phase III study of first-line (1L) inavolisib/placebo + a CDK4/6 inhibitor + letrozole (INAVO/PBO + CDK4/6i + LET) in participants (pts) with PIK3CA-mutated (mut), hormone receptor-positive (HR+), HER2-negative (HER2-), endocrine-sensitive advanced breast cancer (aBC) (ESMO-BC 2025) - P2/3, P3 | "INAVO120 (NCT04191499) showed that 1L treatment with INAVO + palbociclib (PALBO) + fulvestrant (FULV) resulted in a significantly improved progression-free survival (PFS) benefit v PBO + PALBO + FULV (stratified hazard ratio 0.43; 95% confidence interval [CI] = 0.32–0.59; p200 centres, globally."

Clinical • Metastases • P3 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 • CDK4 • HER-2 • PIK3CA

Optimizing post-CDK4/6i strategies in HR+/HER2− metastatic breast cancer: A network meta-analysis of emerging therapies (ESMO-BC 2025) - "The findings showed that venetoclax plus fulvestrant demonstrated the strongest survival benefit among second-line and later HR+/HER2− MBC post-CDK4/6i therapies. Inavolisib and entinostat showed potential but require further validation. The limited efficacy of elacestrants suggests they may not be a preferred choice post-CDK4/6i."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Development and evaluation of a novel non-competitive MAGLUMI estradiol chemiluminescence immunoassay. (PubMed, Clin Chim Acta) - "The cross-reactivity with estrone, estriol, fulvestrant, abemaciclib and estradiol valerate is notably minimized. Meanwhile, the quantification result of this system strongly correlates with LC-MS/MS (y = 1.008x + 0.8949, R2 = 0.981). In conclusion, the non-competitive reagents developed in this study for estradiol detection outperform existing competitive reagents, providing more reliable results for clinical applications."

Journal

Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Chinese Men and Postmenopausal Women With Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=69 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2025 ➔ Mar 2026 | Trial primary completion date: Aug 2025 ➔ Mar 2026

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

Effect of atirmociclib plus endocrine therapy (ET) on serum thymidine kinase activity (TKa) in a phase I study of patients with HR+/HER2− metastatic breast cancer (mBC) (ESMO-BC 2025) - P1 | "Here, we evaluated the effect of atirmociclib + ET on serum TKa and its relationship with progression-free survival (PFS) in pts with prior CDK4/6i use in Parts 1B (300 mg/400 mg atirmociclib BID + letrozole) and 1C (300 mg/400 mg atirmociclib BID + fulvestrant), and treatment-naïve pts in Part 2B (300 mg atirmociclib BID + letrozole). Blood samples were collected at baseline (Cycle 1 Day 1 [C1D1]), C1D15 and C2D1. In this phase I study, atirmociclib + ET achieved strong inhibition of TKa in pts with HR+/HER2− mBC, demonstrating PD effects. Overall, lower baseline TKa was associated with longer PFS. Pts with sustained complete inhibition of TKa tended to have longer PFS, suggesting that deeper CDK4 target modulation by atirmociclib may lead to improved clinical outcomes."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK6 • HER-2

Mecapegfilgrastim for the Prevention of Dalpiciclib -Induced Neutropenia in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=132 | Active, not recruiting | Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2023 ➔ Jan 2025

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

A Novel B7-H4xCD3 Bispecific T Cell Engager (PF-07260437) Synergizes with Breast Cancer Standard of Care and Immune-Checkpoint Therapies. (PubMed, Mol Cancer Ther) - "Additionally, combining PF-07260437 with standard of care (palbociclib plus fulvestrant) and a checkpoint inhibitor (anti-PD-1) showed combinatorial benefits in an immune competent in vivo model. Finally, the manageable toxicity profile of PF-07260437 was highlighted in an exploratory toxicology study in cynomolgus monkeys. These data support the clinical testing of PF-07260437 for treating B7-H4 expressing solid tumors, including breast cancer."

IO biomarker • Journal • Breast Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • CD8 • VTCN1

Clinical aspect of male breast cancer: a burgeoning and unaddressed issue. (PubMed, Mol Biol Rep) - "Topics covered include aromatase inhibitors, fulvestrant, and the prolactin and androgen receptor targeting pathways, as well as the therapeutic therapy of male breast cancer. Endocrine treatment, which includes tamoxifen, aromatase inhibitors, and GnRH analogues, as well as cytotoxic chemotherapy, are characterized in light of the existing research. We also outline the possible function of targeted medications such as HER2-directed treatments, PARP inhibitors, and angiogenesis inhibitors."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Male Breast Cancer • Oncology • Solid Tumor • AR • BRCA1 • BRCA2 • CHEK2 • HER-2

Baseline ctDNA and methylation status as predictors of treatment benefit in the phase III post MONARCH trial of abemaciclib + fulvestrant in advanced breast cancer patients (ESMO-BC 2025) - P3 | "Within multiple biomarker subgroups, abemaciclib had consistent benefit. These exploratory results are hypothesis generating and offer further insight into the use of abemaciclib + fulvestrant as a treatment option for HR+, HER2- ABC after progression on CDK4/6i."

Circulating tumor DNA • Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Imlunestrant (Imlu) with or without abemaciclib (Abema) in advanced breast cancer (ABC): A subgroup analysis in CDK4/6 inhibitor (CDK4/6i)-pretreated patients (pts) from EMBER-3 (ESMO-BC 2025) - P3 | "The EMBER-3 trial reported significant PFS improvement with imlu over standard therapy (SOC; fulvestrant [fulv] or exemestane) in pts with ESR1 mutations (m), as well as with imlu + abema over imlu in all pts, regardless of ESR1m. In pts with ER+, HER2- ABC who have progressed on prior CDK4/6i, imlu+abema showed a consistent benefit over imlu, regardless of clinico-genomic factors. EMBER-3 is the 1st phase III trial to show benefit of an oral SERD + CDK4/6i after disease progression on prior CDK4/6i."

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Dynamic Brain [18F] fluoroestradiol (FES) PET Acquisition Protocol Optimization for Improved Detection of Breast Cancer Brain Metastases (SNMMI 2025) - "Exclusion criteria were active treatment with ER degraders or modifiers (Tamoxifen, Fulvestrant) as per FES appropriate use guidelines. Five patients were included in this study, with a total of 18 lesions. The 60-75 minutes-p.i. dataset had the highest LDR of 78% (14/18 lesions), followed by the 75-90 minutes-p.i."

Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Targeting Estrogen Receptor Potentiates Responsiveness to PD-1 Blockade by Inducing HMGB1 SUMOylation (IMMUNOLOGY 2025) - "Using an immunocompetent ER+ mouse BC model, we demonstrated that combination therapy of fulvestrant, an ER antagonist, and chemotherapy potentiates responsiveness to PD-1blockade via HMGB1. Mechanically, ER directly interacts with HMGB1 and inhibits its SUMOylation and thereby release from the nucleus. Overall, combining ER antagonists and chemotherapy can potentially unleash the clinical benefit of ICIs.Keywords: Animals Human; Molecules Chemokines Cytokines; Processes Cytotoxicity; Techniques/Approaches Transgenic/Knockout Mice"

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HMGB1

Multi-cohort cross-omics analysis reveals disease mechanisms and therapeutic targets in HTLV-1-associated myelopathy, a neglected retroviral neuroinflammatory disorder. (PubMed, Res Sq) - "In silico drug screening identified estrogen blocker Fulvestrant as the top hit, while also confirming existing (pre)clinical data for HDAC inhibitors and immunosuppressants...In conclusion, our data-driven approach uncovers novel disease mechanisms and therapeutic targets, and a validated polygenic risk score allowing targeted surveillance for high-risk individuals. A strong molecular overlap to other neurodegenerative/neuroinflammatory diseases reveals shared neuropathogenic pathways between unrelated viruses."

Journal • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Metabolic Disorders • Multiple Sclerosis • Psychiatry • Solid Tumor • APOA1 • CD4

Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: primary results from a two-part, multicentre, single-arm, phase 2a study. (PubMed, Lancet Oncol) - P2 | "Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy-free triplet regimen."

Journal • P2a data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

ALISCA-Breast1: A phase II study of ALISertib in combination with endocrine therapy in patients with hormone receptor-positive (HR+), HER2-negative (HER2–) recurrent or metastatic breast CAncer (ESMO-BC 2025) - P2 | "Eligible patients are randomized 1:1:1 to alisertib 30, 40, or 50 mg orally bid on d1−3, 8–10, and 15–17 q28d, plus physician's choice of anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen not previously used in recurrent/metastatic setting or progressed upon in adjuvant setting; up to 50 patients will be randomized per arm in the USA and Europe. All biomarkers will be assessed centrally. The study will determine the optimal alisertib dose to combine with ET."

Clinical • Combination therapy • 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 • HER-2

Primary resistance to the endocrine and CDK4/6 inhibitor therapy in postmenopausal women with metastatic breast cancer: An observational case-control study (ESMO-BC 2025) - "The aim of this study was to determine clinicopathological factors associated with primary resistance to fulvestrant and CDK4/6i combination in real-world setting. The retrospective secondary data analysis from 31/05/2019 till 23/05/2023 of patients (pts) diagnosed with mHR+HER2-BC treated with first line CDK4/6i (ribociclib or abemaciclib) and fulvestrant in three major cancer centers in Lithuania was performed. Negative and week PR expression, Ki67 index >25%, more than one mts site and adjuvant HT duration ≤1 year are associated with primary resistance to CDK4/6i and fulvestrant combination in women with mHR+HER2-BC."

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 • ER • HER-2 • PGR

Palbociclib plus endocrine therapy in clinically relevant HR+/HER2- mBC subgroups: A real-world multicenter study (ESMO-BC 2025) - "In this study, we assessed the real-world (rw) efficacy of P plus ET and investigated factors potentially associated with treatment benefit in diverse subgroups of patients (pts). A retrospective multicenter study was conducted involving consecutive HR+/HER2- mBC pts treated with P plus letrozole (L) or fulvestrant (F) between March 2016 and October 2024 at 5 cancer centers in the Campania region of Italy. In this rw study, P plus ET demonstrated consistent efficacy across a broad spectrum of clinically relevant subgroups. Administration in later lines and P dose reduction significantly affected rwPFS, whereas no impact on rwOS was observed. These findings underline the need for tailored strategies to optimize patient outcomes outside the context of controlled clinical trials."

Clinical • Real-world • Real-world evidence • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • HER-2