Elacestrant in ESR1-mutant, endocrine-responsive metastatic breast cancer: should health authorities consider post hoc data to inform priority access?

ESMO Open, Год журнала: 2024, Номер 9(9), С. 103701 - 103701

Опубликована: Сен. 1, 2024

Highlights•HR+/HER2− mBC is the most common disease subtype.•After progression on CDK4/6is, choice of treatment based a biomarker-driven algorithm.•Elacestrant an option for patients with ESR1-mutant and well tolerated.•A subgroup ESR1-mutions specific clinical features can derive meaningful benefit from elacestrant.AbstractFor hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2−) metastatic breast cancer (mBC) progressed first-line endocrine therapy plus cyclin-dependent kinase 4 6 inhibitor (CDK4/6i), fulvestrant, selective estrogen degrader (SERD) administered intramuscularly, represented only monotherapy until approval elacestrant. This oral SERD has been approved HR+/HER2− by European Medicines Agency, Food Drug Administration, UK Healthcare products Regulatory according to results randomized phase III EMERALD trial, which demonstrated elacestrant superiority over standard monotherapy.Consequently, incorporated in Society Medical Oncology American Clinical guidelines. However, Europe, access this recommended drug depends decision National Health Authorities each state.In communication, we describe main implications context algorithm CDK4/6i, conclude that tumors really clinically elacestrant, sparing more toxic combination approaches preserving quality life.

Язык: Английский

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Elacestrant plus alpelisib in an ESR1 and PIK3CA co-mutated and heavily pretreated metastatic breast cancer: the first case report for combination efficacy and safety

Therapeutic Advances in Medical Oncology, Год журнала: 2024, Номер 16

Опубликована: Янв. 1, 2024

Breast cancer (BC) is the leading cause of cancer-related mortality among women, and hormone receptor (HR)-positive subtype makes up majority all cases. The standard care in HR + /HER2 − metastatic BC (MBC) endocrine therapy (ET) plus a CDK4/6 inhibitor (CDK4/6i). ESR1 mutations could impair clinical efficacy ETs. Similarly, PIK3CA may serve as negative prognostic marker. Furthermore, MBC challenging to treat despite new drug approvals. Our patient received multiple lines ET ± CDK4/6i chemotherapy but persistently progressed after each or stopped treatment due adverse events. Here we showed for first time that an all-oral combination elacestrant alpelisib was feasible, tolerable, clinically active co-mutated heavily pretreated patient. We achieved remarkable response lesions with minor toxicity issues. This case highlights importance utilizing up-to-date therapeutic agents reactive decision-making during personalized treatment.

Язык: Английский

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Current Therapeutic Opportunities for Estrogen Receptor Mutant Breast Cancer

Biomedicines, Год журнала: 2024, Номер 12(12), С. 2700 - 2700

Опубликована: Ноя. 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

Язык: Английский

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Molecular Profiling of Endocrine Resistance in HR+/HER2-Metastatic Breast Cancer: Insights from Extracellular Vesicles-Derived DNA and ctDNA in Liquid Biopsies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 13045 - 13045

Опубликована: Дек. 4, 2024

Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge advanced cases. A deeper knowledge of the use liquid biopsy is crucial for implementation precision medicine mBC real-time treatment guidance. Our study assesses prognostic value

Язык: Английский

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Elacestrant Monotherapy as a Second-Line Treatment for ER-Positive, HER2-Negative Advanced Breast Cancer with ESR1 Mutations

EMJ Oncology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 6, 2024

Язык: Английский

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Practical treatment strategies and novel therapies in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2−) advanced breast cancer

ESMO Open, Год журнала: 2024, Номер 9(12), С. 103997 - 103997

Опубликована: Дек. 1, 2024

Mutations in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway occur 30%-40% patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer. For most patients, endocrine therapy a cyclin-dependent 4/6 (CDK4/6) inhibitor is first-line treatment. Recent studies indicate that adding inavolisib, PI3Kα inhibitor, to palbociclib/fulvestrant benefits endocrine-resistant HR+/HER2- metastatic cancer PIK3CA mutation. Alpelisib and capivasertib are both US Food Drug Administration (FDA) approved combination fulvestrant HR+/HER2-, PIK3CA-mutant cancer, activity post-CDK4/6 setting. Capivasertib added first AKT show significant progression-free survival benefit trend for overall only option phosphate tensin homolog (PTEN) or alterations. Toxicity profiles all agents necessitate careful patient selection. Several mutant-selective pan-mutant-selective novel inhibitors under investigation potential improve tolerability efficacy.

Язык: Английский

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The state of the science of oral selective oestrogen receptor degraders

The Lancet Oncology, Год журнала: 2024, Номер 25(11), С. 1388 - 1389

Опубликована: Окт. 30, 2024

Язык: Английский

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Treatment Strategies and Sequencing After Endocrine Therapy Plus CDK4/6 Inhibitors in Patients with ER+/HER2- Advanced/Metastatic Breast Cancer

EMJ Oncology, Год журнала: 2024, Номер unknown, С. 27 - 38

Опубликована: Окт. 29, 2024

This symposium took place on the first day of 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain. The goal was to present recommendations treatment strategies and sequencing patients with oestrogen-receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-), advanced/metastatic breast cancer after first-line (1L) therapy endocrine (ET) plus inhibitors cyclin-dependent kinases 4 6 (CDK4/6i). An expert panel clinicians explained that most will eventually develop resistance ET regimens during setting, they discussed current ESMO second- or later-line (2L+) treatment, which are driven by sensitivity status biomarkers. Trial data support therapeutic this patient population were presented, benefits risks associated different options summarised. emphasised importance testing emergent ESR1 mutations at each progression course, ideally analysing circulating DNA from a liquid biopsy, order identify whom elacestrant be particularly beneficial.

Язык: Английский

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