Imlunestrant with or without Abemaciclib in Advanced Breast Cancer

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

BackgroundImlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations the gene encoding ERα (ESR1).MethodsIn phase 3, open-label trial, we enrolled patients ER-positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer recurred or progressed during after aromatase inhibitor therapy, administered alone cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, imlunestrant–abemaciclib. Primary end points investigator-assessed progression-free survival imlunestrant as compared therapy among ESR1 all imlunestrant–abemaciclib who had undergone randomization concurrently.ResultsOverall, 874 underwent randomization, 331 330 213 Among 256 mutations, median was 5.5 months 3.8 therapy. The estimated restricted mean time at 19.4 7.9 (95% confidence interval [CI], 6.8 9.1) 5.4 CI, 4.6 6.2) (difference, 2.6 months; 95% 1.2 3.9; P<0.001). In overall population, 5.6 (hazard for progression death, 0.87; 0.72 1.04; P=0.12). 426 comparison of 9.4 months, respectively ratio, 0.57; 0.44 0.73; incidence grade 3 higher adverse events 17.1% 20.7% 48.6% imlunestrant–abemaciclib.ConclusionsAmong HER2-negative cancer, treatment led significantly longer than those but not population. Imlunestrant–abemaciclib improved regardless ESR1-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.)

Language: Английский

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Oral SERDs: Transforming the treatment of advanced breast cancer—Insights from EMBER-3

Med, Journal Year: 2025, Volume and Issue: 6(2), P. 100602 - 100602

Published: Feb. 1, 2025

Language: Английский

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Oral selective estrogen receptor degraders (SERDs) in Hormone receptor-Positive HER2-Negative Metastatic breast cancer After Progression with CDK4/6 inhibitors

Expert Review of Anticancer Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC) remains a prevalent and challenging disease. Endocrine therapy (ET) combined with CDK4/6 inhibitors is the first-line standard of care, yet resistance mechanisms, including ESR1 mutations, drive disease progression. Novel oral selective estrogen receptor degraders (SERDs) have emerged as promising therapeutic agents after progression secondary to mutations. However, available studies on SERDs differ in design, study population, outcomes, necessitating critical review data. This explores clinical efficacy, safety profiles HR-positive, mBC, particularly following inhibitors. Recent key trials, EMERALD, SERENA-2, EMBER-3 AMEERA-3, are analyzed, highlighting their efficacy overcoming resistance, especially ESR1-mutant populations. Oral offer enhanced bioavailability convenience compared fulvestrant, representing advancement endocrine therapy. Their integration into treatment strategies, combination regimens ctDNA-driven approaches, may improve patient outcomes address mechanisms. other than refinement for selection limited. Further trials needed optimize SERD use define most effective strategies SERDs.

Language: Английский

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Immune microenvironment and molecular mechanisms in endometrial cancer: implications for resistance and innovative treatments

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 16, 2025

Language: Английский

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Current Therapeutic Opportunities for Estrogen Receptor Mutant Breast Cancer

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2700 - 2700

Published: Nov. 26, 2024

Estrogen receptor α (ERα) drives two out of three breast cancers and therefore ERα is a major therapeutic target for ER-positive cancer patients. Drugs that inhibit activity or block estrogen synthesis in the body are currently being used clinic to treat have been quite successful controlling progression majority However, often becomes resistant these endocrine therapies, leading endocrine-resistant metastatic cancer, very aggressive leads death. Recent large-scale genomic studies revealed series activating somatic mutations gene (ESR1) Of these, Y537S D538G found at much higher rate patients with cancer. Remarkably, produce an transcriptional than wild type absence estradiol, traditional therapy has poor efficacy against ER mutants. Therefore, development new drugs mutants unmet clinical need This review summarizes recent preclinical trials targeting mutant

Language: Английский

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