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Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients.

ABSTRACT: Advanced breast cancer (ABC) that is positive for hormone receptors (HRs) and human epidermal growth factor receptor 2 (HER2) is a cancer subtype with distinctive characteristics. The primary treatment guidelines suggest that a combination therapy comprising anti-HER2 therapy and chemotherapy should be administered as the initial treatment for HR-positive/ HER2-positive (HR+/HER2+) ABC. However, crosstalk between the HR and HER2 pathways can partially account for the resistance of HR+/HER2+ disease to HER2-targeted therapy. This, in turn, provides a rationale for the concomitant administration of HER2-targeted therapy and endocrine therapy (ET). Many clinical studies have confirmed that the combination of HER2-targeted therapy and ET as a first-line treatment is not inferior to the combination of HER2-targeted therapy and chemotherapy, and support its use as a first-line treatment choice for HR+/HER2+ ABC. Other drugs, such as antibody-drug conjugates, cyclin-dependent kinase 4/6 inhibitors, phosphatidylinositol 3-kinase-protein kinase B (AKT)-mammalian target of rapamycin inhibitors, and programmed cell death protein 1 or programmed cell death ligand 1 inhibitors, may also improve the prognosis of patients with breast cancer by blocking signaling pathways associated with tumor proliferation and break new ground for the treatment of HR+/HER2+ ABC.

SUBMITTER: Liang Y

PROVIDER: S-EPMC10771751 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients.

Liang Yuehua Y Liu Xiaoran X Yun Zehui Z Li Kun K Li Huiping H

Therapeutic advances in medical oncology 20240106

Advanced breast cancer (ABC) that is positive for hormone receptors (HRs) and human epidermal growth factor receptor 2 (HER2) is a cancer subtype with distinctive characteristics. The primary treatment guidelines suggest that a combination therapy comprising anti-HER2 therapy and chemotherapy should be administered as the initial treatment for HR-positive/ HER2-positive (HR+/HER2+) ABC. However, crosstalk between the HR and HER2 pathways can partially account for the resistance of HR+/HER2+ dise ...[more]

PMID: 38188468

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Project description:AimTo compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) versus ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa.MethodsThis randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A.ResultsIn cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: not reached versus 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719; p = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm (p < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: 11.5 versus 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588; p < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm (p < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B).ConclusionThe addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population.Trial Registration: ClinicalTrials.gov identifier: NCT02763566.

Project description:Breast cancer (BC) is the most common malignancy in women worldwide, with approximately two-thirds having hormone receptor-positive (HR+) tumors. New endocrine therapy (ET) strategies include combining ET agents as well as adding inhibitors targeting growth factors, angiogenesis, the mechanistic target of rapamycin, phosphoinositide 3-kinase (PI3K), or cyclin-dependent kinase 4/6 to ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib plus letrozole as first-line therapy for HR+/HER- advanced BC with special consideration for the former in ET-naïve patients, as well as everolimus plus exemestane or palbociclib plus fulvestrant as second-line therapy with special consideration in select first-line patients. Although the safety profiles of these combinations are generally predictable and manageable, both everolimus and palbociclib are associated with an increased risk of potentially serious or early-onset toxicities requiring individualized a priori adverse event risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Although each of these combinations improves progression-free survival, none with the exception of anastrazole plus fulvestrant have demonstrated improved overall survival. PI3K catalytic-? mutations assessed from circulating tumor DNA represent the first potentially viable serum biomarker for the selection of ET combinations, and new data demonstrate the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis. Therapeutic ratios of select ET combinations support their use in first- and second-line settings, but optimal sequencing has yet to be determined.2017;22:12-24 IMPLICATIONS FOR PRACTICE: Emerging data show that new endocrine therapy (ET) combinations can improve progression-free and overall survival outcomes in patients with hormone receptor-positive, HER2-negative (HR+/HER-) advanced breast cancer. Level 1 evidence supports consideration of dual ET regimens, particularly in ET-naïve patients, or palbociclib plus letrozole as first-line therapy, as well as the addition of mTOR or CDK4/6 inhibitors to established ET in the second-line setting and in select first-line patients. Some combinations are associated with increased risk of class-specific toxicities that will require individualized risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Recent data on a noninvasive biomarker assay that predicts response to a phosphoinositide 3-kinase inhibitor demonstrates the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis.

Dataset Information

Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients.

Publications

Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients.

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