Orserdu (elacestrant) / Radius, Menarini, DRI Healthcare, SciClone - LARVOL DELTA

Detection of ESR1 Mutations in Tissue and Liquid Biopsy with Novel Next-Generation Sequencing and Digital Droplet PCR Assays: Insights from Multi-Center Real Life Data of Almost 6000 Patients. (PubMed, Cancers (Basel)) - "Our findings not only corroborate prior research concerning the rarity of these mutations in unselected patients but also emphasize the importance of robust and broad molecular assays rather than single gene assays in their detection and characterization in the diagnostic setting. Advantages of different approaches are discussed to address the current clinical need."

Biomarker • Journal • Liquid biopsy • Next-generation sequencing • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AKT1 • BRCA1 • BRCA2 • ER • HER-2 • PIK3CA • TP53

Lasofoxifene acts as a selective agonist in the bone microenvironment (ENDO 2025) - P3 | "ELAINE-III [NCT05696626] is a clinical trial currently investigating the efficacy of lasofoxifene and abemaciclib compared to fulvestrant abemaciclib combination therapy for advanced or metastatic ER+ breast cancer with an ESR1-mutation...Additionally, drug synergism studies with lasofoxifene and the NCI NExT Oncology Interrogation Tools Set of 555 drugs were performed to identify pathways which were vulnerable in Elacestrant-treated cells...This study has determined that lasofoxifene is protective in the bone microenvironment, unlike other new-generation endocrine therapies, and future directions include evaluating the ramifications of this activity on bone metastasis progression.*. .*"

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

The impact of ethnicity on benefit from novel drugs approved for breast cancer treatment: a systematic review and meta-analysis of randomized phase 3 trials of the last decade. (SABCS 2024) - "23 phase III RCTs were identified in the aBC setting, with 1547 (11.1%) patients of Asian ethnicity. Experimental drugs tested included CDK4/6i (palbociclib, ribociclib, abemaciclib), SERD (elacestrant), PI3Ki (alpelisib), PARPi (olaparib, talazoparib), broad variety of anti-HER2 drugs (tucatinib, trastuzumab deruxtecan, pertuzumab, T-DM1, neratinib, margetuximab), anti-PD-1 and anti-PD-L1 drugs (pembrolizumab, atezolizumab) and anti-TROP2 drug (sacituzumab govitecan). 16 RCTs provided HR (95%CI) for PFS in the subgroup of Asians and 17 RCTs for Non-Asians."

IO biomarker • P3 data • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Screening or Early Detection of Brain Metastases and the Treatment in the Era of New Agents (GBCC 2025) - "Advances in systemic therapy have been greatest in HER2-positive breast cancer, where the current NCCN guidelines include a growing list of CNS-active regimens, such as tucatinib-capecitabine-trastuzumab, T-DXd, T-DM1, high dose trastuzumab and pertuzumab, neratinib-capecitabine, and lapatinib-capecitabine...There are a number of novel blood-brain-barrier (BBB) penetrant HER2-targeted tyrosine kinase inhibitors (e.g. ZN1041, IAM1363) in early-phase clinical trials. For patients with HER2-negative tumors, the data are more sparse; however, activity of chemotherapy drugs such as capecitabine, anthracyclines, platinums, and eribulin has been reported...Ongoing clinical trials are testing a wide variety of ADCs, such as patritumab deruxtecan, datopotamab deruxtecan, ARX788, and others...For example, the ELECTRA trial is testing the combination of elacestrant and abemaciclib. Overall, the expanding array of systemic options with clinically meaningful intracranial activity, as..."

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 • Triple Negative Breast Cancer • ER • HER-2

Real-World Study of ESR1 Mutation Testing by Liquid Biopsy Using Digital PCR or NGS to Guide Elacestrant Use in Metastatic Breast Cancer Patients (ESMO-BC 2025) - No abstract available

Biopsy • Clinical • Liquid biopsy • Metastases • Next-generation sequencing • Real-world • Real-world evidence • Breast Cancer • Oncology • Solid Tumor • ER

ELEGANT: Elacestrant versus standard endocrine therapy (ET) in women and men with node-positive, estrogen receptor-positive (ER+), HER2-negative (HER2-), early breast cancer (eBC) with high risk of recurrence in a global, multicenter, randomized, open-label phase 3 study (AACR 2025) - P3 | "Given that elacestrant demonstrated efficacy in mBC regardless of ESR1-mut status relative to SOC ET and has shown biologic activity in eBC, it is hypothesized that elacestrant can prolong invasive breast cancer-free survival (IBCFS) in pts with high-risk eBC who received prior adj ET±CDK4/6i.Design and ELEGANT (NCT06492616) is a global, multicenter, open-label phase 3 study designed to evaluate elacestrant vs SOC ET (AI or tamoxifen) in pts with eBC and a high risk of recurrence. The primary endpoint is IBCFS. Key secondary endpoints include DRFS, OS, IDFS, safety, PROs-QoL, and PK.Status: Planned enrollment is 4,220 patients; recruitment is ongoing."

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • ER • HER-2

ELCIN: Elacestrant (Ela) in women and men with CDK4/6 inhibitor (CDK4/6i)- naive estrogen receptor- positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study (AACR 2025) - P2 | "Secondary objectives are ORR, DoR, CBR, OS, PROs-QoL, and safety. Exploratory objectives include Ela efficacy according to ESR1-mut status, changes in biomarkers, including allele mutation frequencies (cfNAs), and relationship between efficacy endpoints.Status: ELCIN has a planned sample size of 60 pts; recruitment is ongoing worldwide."

Clinical • Metastases • P2 data • 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 • Solid Tumor • CDK4 • ER • HER-2 • mTOR

ADELA: A double-blind, placebo-controlled, randomized phase 3 trial of elacestrant (ELA) + everolimus (EVE) versus ELA + placebo (PBO) in ER+/HER2- advanced breast cancer (aBC) patients with ESR1-mutated tumors progressing on endocrine therapy (ET) + CDK4/6i. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT06382948 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Elacestrant combinations in patients (pts) with ER+/HER2- locally advanced or metastatic breast cancer (mBC): Safety update from ELEVATE, a phase (Ph) 1b/2, open-label, umbrella study. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05563220 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Elacestrant (Ela) combinations with ribociclib (Ribo) and everolimus (Eve) in patients (pts) with ER+/HER2- locally advanced or metastatic breast cancer (mBC): Update from ELEVATE, a phase (Ph) 1b/2, open-label, umbrella study. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05563220 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC)—An open-label multicenter phase 2 study. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05596409 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA). (ASCO 2025) - "Clinical Trial Registration Number: 2022-501453-36-00 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Circulating tumor DNA • Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

ELEGANT: Elacestrant versus standard endocrine therapy (ET) in women and men with node-positive, estrogen receptor-positive (ER+), HER2-negative (HER2-), early breast cancer (eBC) with high risk of recurrence in a global, multicenter, randomized, open-label phase 3 study. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT06492616 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

ET-Based Combinations and Novel Agents in HR+/HER2- Advanced Breast Cancer (GBCC 2025) - "Tumors with alterations in the PIK3CA/AKT/PTEN pathway may be offered a pathway inhibitor such as capivasertib or alpelisib, and patients with high risk recurrence of HR+ disease with a PIK3CA mutation may benefit from early introduction of a first-line inavolisib triplet...The oral SERD elacestrant is approved as monotherapy in pretreated patients with tumors harboring an ESR1 mutation. Additional oral SERDs, including imlunestrant, camizestrant, and giredestrant, have demonstrated activity and are in registrational trials. An additional maneuver in the pretreated space includes continuation of a CDK4/6 inhibitor after prior CDK4/6 inhibitor, with activity seen from switching to abemaciclib or ribociclib from a prior agent, and novel CDK inhibitors are in trials as a next generation approach. The mTOR inhibitor everolimus remains an option for pretreated patients as well, particularly when actionable mutations are not present. The continued introduction of novel agents..."

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 • PIK3CA

Effect of Tasurgratinib as an Orally Available FGFR1-3 Inhibitor on Resistance to a CDK4/6 Inhibitor and Endocrine Therapy in ER+/HER2- Breast Cancer Preclinical Models. (PubMed, Cancers (Basel)) - "FGF signaling plays a role in resistance to CDK4/6 inhibitors and ET in ER+ BC. Tasurgratinib has the potential to exhibit significant antitumor activity in combination with ET against ER+ BC via FGF signaling inhibition. These findings indicate the therapeutic potential of tasurgratinib in treating ER+ BC."

Journal • Preclinical • Breast Cancer • Endocrine Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • FGF10 • FGF2 • FGFR1 • HER-2

ELEGANT: Elacestrant VS Standard Endocrine Therapy in Women and Men With Node-Positive, Estrogen Receptor-Positive, HER2- Negative, Early Breast Cancer With High Risk of Recurrence in a Global, Multicenter, Randomized, Open-Label Phase 3 Study (MBCC 2025) - P3 | "Materials and Methods ELEGANT (NCT06492616) is a global, multicenter, open-label phase 3 study designed to evaluate elacestrant vs SOC ET (aromatase inhibitor or tamoxifen) in patients with EBC and a high risk of recurrence. Key secondary end points include distant relapse-free survival, overall survival, invasive disease-free survival, safety, patient-reported outcomes-quality of life, and pharmacokinetics. Status Planned enrollment is 4220 patients; recruitment is ongoing."

Clinical • P3 data • 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 • Inflammatory Breast Cancer • Oncology • Solid Tumor • ER • HER-2

ELCIN: Elacestrant in Women and Men With CDK4/6 Inhibitor-Naive Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer: An Open-Label, Multicenter, Phase 2 Study (MBCC 2025) - P2, P3 | "Exploratory objectives include elacestrant efficacy according to ESR1 mutation status, changes in biomarkers, including allele mutation frequencies (cfNAs), and the relationship between efficacy end points. Status ELCIN has a planned sample size of 60 patients; recruitment is ongoing worldwide."

Clinical • Metastases • P2 data • 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 • Solid Tumor • ER • HER-2 • mTOR

Elacestrant Plus Abemaciclib Combination in Patients With Estrogen Receptor-positive, HER2-Negative Advanced or Metastatic Breast Cancer (MBCC 2025) - P1/2, P3 | "Elacestrant has the potential to become the ET backbone to enable an all-oral treatment option, delay chemotherapy or antibody-drug conjugate–based regimens. Phase 2 is ongoing."

Clinical • Metastases • Anemia • Breast Cancer • Constipation • Estrogen Receptor Positive Breast Cancer • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • ER • HER-2

Elacestrant vs Standard of Care in ER+, HER2- Advanced or Metastatic Breast Cancer With ESR1-Mutated Tumors: ESR1 Allelic Frequencies and Clinical Activity From the Phase 3 EMERALD Trial (MBCC 2025) - P3 | "A longer PFS benefit was observed with elacestrant vs SOC in patients with tumors harboring coexisting ESR1 and PIK3CA mutations despite 89% of patients having a lower ESR1-mutation VAF compared with PIK3CA-mutation VAF. In patients with ER+/HER2– mBC who received a longer duration of prior ET plus CDK4/6i and with tumors harboring coexisting ESR1 and PIK3CA mutations, elacestrant can be used before PI3K/AKTi, chemotherapy, or antibody-drug conjugate-based regimens."

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 • ER • HER-2 • PIK3CA

Elacestrant Real-World Progression-Free Survival of Adult Patients With ER+/HER2–, Advanced Breast Cancer: A Retrospective Analysis Using Insurance Claims in the United States (MBCC 2025) - P3 | "This study aims to describe the real-world PFS of elacestrant overall and in patients with no prior exposure to fulvestrant, only 1 to 2 lines of ET, 3 or more lines of ET, and/or visceral metastases. Conclusion In a real-world setting, elacestrant showed a consistent real-world PFS benefit among all patients with ER+/HER2– metastatic breast cancer and across clinically relevant subgroups. The real-world PFS with elacestrant exceeded the overall median PFS in EMERALD and is longer when patients are treated in earlier lines."

Metastases • Real-world • Real-world evidence • Reimbursement • Retrospective data • US reimbursement • 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 • Solid Tumor • ER • HER-2

ADELA: A Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial of Elacestrant + Everolimus vs Elacestrant + Placebo in ER+/HER2– Advanced Breast Cancer Patients With ESR1-Mutated Tumors Progressing on Endocrine Therapy (MBCC 2025) - P1/2, P3 | "Patients will receive dexamethasone mouthwash during the first 8 weeks. Secondary end points included investigator-assessed PFS, overall survival, overall response rate, clinical benefit rate, duration of response, time to response, the best percentage change in tumor burden, safety, and health-related quality of life. Status Planned enrollment is 240 patients; recruitment is ongoing."

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 • ER • HER-2

Elacestrant Combinations in Patients With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer: Update From ELEVATE, a Phase 1b/2, Open-Label, Umbrella Study (MBCC 2025) - P1/2, P3 | "To address various resistance mechanisms, the phase 1/2 ELEVATE trial (NCT05563220) evaluates elacestrant with everolimus, alpelisib, capivasertib, ribociclib, palbociclib, or abemaciclib. Conclusion The evaluated combinations continue to demonstrate a known safety profile consistent with each drug plus SOC ET and no increased risk of associated AEs. Elacestrant has the potential to become the ET partner for multiple targeted agents, providing an all-oral treatment option in patients with ER+/HER2– metastatic breast cancer, delaying chemotherapy or antibody-drug conjugate– based regimens."

Clinical • Metastases • P1/2 data • Breast Cancer • Constipation • Dental Disorders • Diabetes • Estrogen Receptor Positive Breast Cancer • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Stomatitis • ER • HER-2

Post-progression treatment options after CDK4/6 inhibitors in hormone receptor-positive, HER2-negative metastatic breast cancer. (PubMed, Cancer Treat Rev) - "Endocrine therapies, including fulvestrant and novel oral selective estrogen receptor degraders (SERDs) like elacestrant, show promise, especially in patients with ESR1 mutations. Targeted therapies such as PI3K/AKT/mTOR inhibitors, exemplified by alpelisib and capivasertib, offer potential by addressing downstream signaling pathways involved in resistance. Additionally, FGFR inhibitors like erdafitinib are under investigation for their role in overcoming specific resistance mechanisms...Ongoing clinical trials are expected to provide deeper insights, guiding the development of more effective post-progression therapeutic strategies. This evolving landscape highlights the need for continuous research and individualized patient care to improve survival and quality of life in HR + mBC patients."

IO biomarker • Journal • Review • 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

Circulating Tumor DNA: TBCRC-068 (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Yale University

Circulating tumor DNA • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Clinical Actionability of Molecular Targets in Multi-Ethnic Breast Cancer Patients: A Retrospective Single-Institutional Study. (PubMed, Mol Diagn Ther) - "In this study, a total of 784 clinically actionable mutations were reported for 1010 patients with genomic sequencing. Of these, 96/1010 (10%) patients had at least one actionable mutation in homologous recombination repair genes (BRCA1, BRCA2, PALB2) and 36/96 (37.5%) patients received PARP inhibitors (33 olaparib and three talazoparib). In addition, 381/1010 (38%) patients had at least one clinically actionable PIK3CA mutation, and 84/381 (22%) received alpelisib. Additionally, 544/1010 (54%) of patients had either AKT1 (41/1010), PIK3CA (381/1010), or PTEN (122/1010) alterations that were FDA approved in November 2023 for capivasertib in the treatment of HR+HER2- metastatic BC (MBC) patients. Furthermore, 144/1010 (14%) patients in this study had at least one ESR1 mutation, a clinically actionable mutation that was FDA approved in January 2023 for elacestrant in the treatment of ER+HER2- MBC patients (44% detected by liquid biopsy). Future studies are needed to..."

Journal • Retrospective data • Tumor mutational burden • 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 • Triple Negative Breast Cancer • AKT1 • ARID1A • BRCA1 • BRCA2 • CCND1 • CDH1 • CDKN2A • CHEK2 • ER • FGF19 • FGF3 • FGF4 • FGFR1 • GATA3 • HER-2 • HRD • KMT2C • MAP3K1 • MCL1 • NF1 • PALB2 • PIK3CA • PTEN • RB1 • TMB • TP53 • ZNF703