Trastuzumab deruxtecan: An antibody-drug conjugate embracing its destiny in breast cancer

Makhlin, Igor; DeMichele, Angela

doi:10.1016/j.xcrm.2022.100668

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…This study showed that, compared with T-DM1, trastuzumab deruxtecan (T-DXd) significantly reduced the risk of progression or death by 72 % (HR 0.28, 95 % CI 0.22%–0.37%) in HER2-positive advanced breast cancer patients who progressed after previous trastuzumab treatment. 28 , 29 , 30 Based on this, T-DXd has become the new second-line standard anti-HER2 therapy in European and American countries. T-DXd has already been approved for the treatment of patients with HER2-positive advanced breast cancer in China; however, the exorbitant price limits its extensive clinical application.…”

Section: Discussionmentioning

confidence: 99%

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer: A single-arm phase 2 clinical trial

Jin,

Xu,

Wang

et al. 2024

Cancer Pathogenesis and Therapy

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Section: Discussionmentioning

confidence: 99%

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer: A single-arm phase 2 clinical trial

Jin,

Xu,

Wang

et al. 2024

Cancer Pathogenesis and Therapy

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“…T-DXd is a combination of a high drug antibody ratio (DAR) of eight molecules per antibody, plasma-stable linker that is selectively cleaved by tumor lysosomal proteases, and membrane-permeable payload. It is able to diffuse out into neighboring cells, thereby addressing tumor heterogeneity with a ''bystander'' effect, hence leading to impressive response rates in various HER2-expressing cancers including breast, lung, and gastric tumors [43]. In phase 3 trial of the drug involving patients with HER2-low metastatic breast cancer, T-DXd resulted in significantly longer progression-free and overall survival than the clinicians' choice of chemotherapy [44].…”

Section: Discussionmentioning

confidence: 99%

Development of Nomogram for Predicting Axillary Pathologic Complete Response after Neoadjuvant Therapy in Breast Cancer Patients without Distant Metastasis

Zhang,

Cao,

Wang

et al. 2023

Preprint

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(1) Background: For N+ breast cancer patients treated with neoadjuvant therapy, the response to the treatment, especially the probability of axillary pathological complete response (apCR), can guide the choice of subsequent surgical strategy. (2) Method: 50 N+ breast cancer patients were treated with neoadjuvant therapy, with the response to neoadjuvant therapy guiding subsequent surgical modalities. Logistic regression was used to calculate the coefficients of the significant predictors for axillary pathologic complete response (apCR), and a nomogram was developed based on the logistic model and internally validated. (3) Results: 4 variables were found to be related to the probability of apCR: pathological grade and molecular subtype (HER2+), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). The nomogram based predictive cooperating pathological features and hematological test results can be used to predict apCR in N+ breast cancer patients who had received neoadjuvant chemotherapy(NAC). The receiver operating characteristic (ROC) curve for the nomogram model is 0.929 [95% confidence interval (CI): 0.859–0.998], indicating a good discrimination. (4) Conclusion: A comprehensive predictive model using clinical data is a useful tool to predict the probability of apCR in N+ breast cancer patients receiving NAC.

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“…These molecules are stabilized in the plasma by a unique tetrapeptide linker and can be selectively cleaved by enzymes that are upregulated in tumor cells, enabling targeted local delivery of the payload [ 55 ]. Furthermore, the membrane-permeable payloads diffuse into neighboring cells, thereby addressing tumor heterogeneity through a “bystander” effect [ 56 ]. The safety and preliminary efficacy of trastuzumab deruxtecan were investigated in a phase 1 study on HER2-expressing advanced solid tumors [ 57 ].…”

Section: Her2: Beyond Trastuzumabmentioning

confidence: 99%

Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

Kim

2024

J Gastric Cancer

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In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

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Trastuzumab deruxtecan: An antibody-drug conjugate embracing its destiny in breast cancer

Cited by 7 publications

References 8 publications

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer: A single-arm phase 2 clinical trial

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer: A single-arm phase 2 clinical trial

Development of Nomogram for Predicting Axillary Pathologic Complete Response after Neoadjuvant Therapy in Breast Cancer Patients without Distant Metastasis

Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

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