Management of patients with HER2-positive metastatic breast cancer after trastuzumab deruxtecan failure

Antonarelli, Gabriele; Corti, Chiara; Tarantino, Paolo; Salimbeni, Beatrice Taurelli; Zagami, Paola; Marra, Antonio; Trapani, Dario; Tolaney, Sara M.; Cortés, Javier; Curigliano, Giuseppe

doi:10.1016/j.esmoop.2023.101608

Cited by 12 publications

(3 citation statements)

References 82 publications

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“…The research of predictive biomarkers in the DAISY clinical trial revealed a reduction in HER2 expression (in terms of % of stained cells) in a significant proportion of patients with progressive disease, suggesting a potential role for the intensity of HER2 expression. Moreover, this antigen drop was shown to be associated to a specific pattern of spatial distribution of HER2-negative cells determined by T-DXd activity [ 2 , 56 ]. A combined genomic analysis revealed the presence of SLX4 gene mutation in 20% of patients failing T-DXd activity compared to 2% at the baseline, which supports the hypothesis of an acquired molecular mechanism of resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Breast cancer (BC) is the leading cancer in women worldwide in terms of both incidence and mortality [ 1 ]. BC is a heterogeneous disease and can be classified based on hormone receptor (HR) expression and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification [ 2 ]. Although treatment advances have improved prognosis, the metastatic disease remains incurable.…”

Section: Antibody-drug Conjugates In Breast Cancermentioning

confidence: 99%

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Charting the Course in Sequencing Antibody-Drug Conjugates in Breast Cancer

Saltalamacchia,

Torrisi,

De Sanctis

et al. 2024

Biomedicines

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Based on the unprecedented results observed in recent clinical trials, antibody-drug conjugates (ADCs) have revolutionized the treatment algorithm of metastatic breast cancer (mBC). The strategy of sequencing different ADCs in other lines of therapy is highly attractive, but the proportion of patients who have undergone such a strategy in the context of published clinical trials is still limited, especially for modern ADCs. HER2-positive disease is primarily managed with a sequence of different ADCs. Historically, trastuzumab emtansine (T-DM1) has been the most commonly used ADC for both early and metastatic HER2-positive disease. Considering the recent evidence related to trastuzumab deruxtecan (T-DXd), it is expected to assume the role of the main ADC in our clinical practice. Herein, we report a retrospective analysis of the sequence of different ADCs relying on available published data from clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Antibody-drug Conjugates In Breast Cancermentioning

confidence: 99%

Charting the Course in Sequencing Antibody-Drug Conjugates in Breast Cancer

Saltalamacchia,

Torrisi,

De Sanctis

et al. 2024

Biomedicines

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“…ADC-mediated cell death may stimulate the immune response and recruit tumor-infiltrating lymphocytes, promoting the recognition of immune effector cell to "cold" tumors, which is the theoretical basis to support the combination strategy with immune checkpoint inhibitor. The combination of antiangiogenic drugs can promote the delivery of ADCs to tumor tissues by normalizing tumor blood vessels to enhance the cell-killing effect 50. Clinical studies on combination therapies should consider all potential benefits and toxicities.…”

mentioning

confidence: 99%

Antibody drug conjugates in breast cancer in China: Highlights, challenges, and prospects

Li,

Jiang

2023

Cancer

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Antibody drug conjugates (ADCs) are novel drugs that exert specific cytotoxicity against tumor cells. China approved T‐Dxd in May 2023, and their introduction has changed the nation’s clinical practice. Although more than 700 ADCs are being investigated worldwide, the challenges that remain in antibody engineering, drug discovery, safety management, resistance, drug selection, and sequencing hinder the further promotion and application of ADCs. Experts in China have discussed the several critical concerns related to clinical practice since 2022. Here, the authors conducted a review of ADCs and then discussed several ADCs explored in China. This study proposes several solutions and strategies to maximize the potential benefit that ADCs can provide to patients with breast cancer.

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Clinical applications of next‐generation sequencing‐based ctDNA analyses in breast cancer: defining treatment targets and dynamic changes during disease progression

Klocker,

Hasenleithner,

Bartsch

et al. 2024

Molecular Oncology

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The advancements in the detection and characterization of circulating tumor DNA (ctDNA) have revolutionized precision medicine and are likely to transform standard clinical practice. The non‐invasive nature of this approach allows for molecular profiling of the entire tumor entity, while also enabling real‐time monitoring of the effectiveness of cancer therapies as well as the identification of resistance mechanisms to guide targeted therapy. Although the field of ctDNA studies offers a wide range of applications, including in early disease, in this review we mainly focus on the role of ctDNA in the dynamic molecular characterization of unresectable locally advanced and metastatic BC (mBC). Here, we provide clinical practice guidance for the rapidly evolving field of molecular profiling of mBC, outlining the current landscape of liquid biopsy applications and how to choose the right ctDNA assay. Additionally, we underline the importance of exploring the clinical relevance of novel molecular alterations that potentially represent therapeutic targets in mBC, along with mutations where targeted therapy is already approved. Finally, we present a potential roadmap for integrating ctDNA analysis into clinical practice.

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Management of patients with HER2-positive metastatic breast cancer after trastuzumab deruxtecan failure

Cited by 12 publications

References 82 publications

Charting the Course in Sequencing Antibody-Drug Conjugates in Breast Cancer

Charting the Course in Sequencing Antibody-Drug Conjugates in Breast Cancer

Antibody drug conjugates in breast cancer in China: Highlights, challenges, and prospects

Clinical applications of next‐generation sequencing‐based ctDNA analyses in breast cancer: defining treatment targets and dynamic changes during disease progression

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