Trastuzumab Deruxtecan Improves Progression-Free Survival and Intracranial Response in Patients with HER2-Positive Metastatic Breast Cancer and Brain Metastases

Jacobson, Anne

doi:10.1093/oncolo/oyac009

Cited by 25 publications

(10 citation statements)

References 2 publications

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“… 40 , 41 , 42 In patients with stable BMs, both the DESTINY-Breast01 as well as the DESTINY-Breast03 demonstrated remarkable levels of intracranial ORR, with 58.3% (95% CI: 36.6%-77.9%) and 67.4%, respectively. 43 , 44 These data further confirmed T-DXd as a valid therapeutic option in this patient population with an unmet medical need.…”

Section: Antibody–drug Conjugates For the Treatment Of Her2-positive ...mentioning

confidence: 60%

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

et al. 2023

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Section: Antibody–drug Conjugates For the Treatment Of Her2-positive ...mentioning

confidence: 60%

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

et al. 2023

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“…Evidence from the DESTINY-Breast03 study showed that the confirmed CNS ORR was 63.8% for T-DXd versus 33.3% for T-DM1. However, it should be pointed out that only patients with stable brain metastases were eligible in this trial and the type of local interventions as well as brain lesion radiotherapy status were not available [48]. A recent pooled analysis from the DESTINY-Breast01-02-03 trials of T-Dxd in patients with HER2-positive metastatic breast cancer having both treated and untreated brain metastases (BMs) at baseline (n = 148) reported an intracranial objective response rate (IC-ORR; i.e., CR and PR in brain lesions) in 45.2% and 45.5% of the patients with treated and untreated brain metastases, respectively.…”

Section: Trastuzumab Deruxtecanmentioning

confidence: 99%

Current Status and Future Perspectives of Antibody–Drug Conjugates in Hormone Receptor-Positive Breast Cancer

Grammoustianou,

Dimitrakopoulos,

Koutras

2024

Cancers

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Breast cancer is the most common cancer type in women. The vast majority of breast cancer patients have hormone receptor-positive (HR+) tumors. In advanced HR+ breast cancer, the combination of endocrine therapy with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors is considered the standard of care in the front-line setting. Nevertheless, resistance to hormonal therapy and CDK4/6 inhibitors eventually occurs, leading to progression of the disease. Antibody–drug conjugates (ADCs) comprise a promising therapeutic choice with significant efficacy in patients with HR+ breast cancer, which is resistant to endocrine treatment. ADCs typically consist of a cytotoxic payload attached by a linker to a monoclonal antibody that targets a specific tumor-associated antigen, offering the advantage of a more selective delivery of chemotherapy to cancer cells. In this review, we focus on the ADC mechanisms of action, their toxicity profile and therapeutic uses as well as on related biomarkers and future perspectives in advanced HR+ breast cancer.

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“…The highly selective anti‐HER2 tyrosine kinase inhibitor tucatinib plus capecitabine and trastuzumab resulted in significantly better PFS and OS as compared with placebo plus capecitabine and trastuzumab in the overall population and in patients with brain metastases who were pretreated with trastuzumab, pertuzumab, and T‐DM1, as indicated by the HER2CLIMB study [ 213 ]. Pyrotinib and T‐DXd also showed impressive efficacy in HER2‐positive patients with brain metastases (Table 3 ) [ 209 , 214 , 215 , 216 , 217 , 218 , 219 ]. The development of novel anti‐HER2 drugs will expand the arsenal for treating HER2‐positive breast cancer patients, for whom continuous anti‐HER2 treatment is essential.…”

Section: Mbcmentioning

confidence: 99%

Breast cancer: an up‐to‐date review and future perspectives

Hong

2022

Cancer Communications

133

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Breast cancer is the most common cancer worldwide. The occurrence of breast cancer is associated with many risk factors, including genetic and hereditary predisposition. Breast cancers are highly heterogeneous. Treatment strategies for breast cancer vary by molecular features, including activation of human epidermal growth factor receptor 2 (HER2), hormonal receptors (estrogen receptor [ER] and progesterone receptor [PR]), gene mutations (e.g., mutations of breast cancer 1/2 [BRCA1/2] and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha [PIK3CA]) and markers of the immune microenvironment (e.g., tumor‐infiltrating lymphocyte [TIL] and programmed death‐ligand 1 [PD‐L1]). Early‐stage breast cancer is considered curable, for which local‐regional therapies (surgery and radiotherapy) are the cornerstone, with systemic therapy given before or after surgery when necessary. Preoperative or neoadjuvant therapy, including targeted drugs or immune checkpoint inhibitors, has become the standard of care for most early‐stage HER2‐positive and triple‐negative breast cancer, followed by risk‐adapted post‐surgical strategies. For ER‐positive early breast cancer, endocrine therapy for 5‐10 years is essential. Advanced breast cancer with distant metastases is currently considered incurable. Systemic therapies in this setting include endocrine therapy with targeted agents, such as CDK4/6 inhibitors and phosphoinositide 3‐kinase (PI3K) inhibitors for hormone receptor‐positive disease, anti‐HER2 targeted therapy for HER2‐positive disease, poly(ADP‐ribose) polymerase inhibitors for BRCA1/2 mutation carriers and immunotherapy currently for part of triple‐negative disease. Innovation technologies of precision medicine may guide individualized treatment escalation or de‐escalation in the future. In this review, we summarized the latest scientific information and discussed the future perspectives on breast cancer.

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Trastuzumab Deruxtecan Improves Progression-Free Survival and Intracranial Response in Patients with HER2-Positive Metastatic Breast Cancer and Brain Metastases

Abstract: In the phase III DESTINY-Breast03 trial, trastuzumab deruxtecan improved progression-free survival (PFS) relative to trastuzumab emtansine across all patients with HER2-positive metastatic breast cancer, including a 75% improvement in PFS among those with baseline brain metastases.

Cited by 25 publications

References 2 publications

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

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

Current Status and Future Perspectives of Antibody–Drug Conjugates in Hormone Receptor-Positive Breast Cancer

Breast cancer: an up‐to‐date review and future perspectives

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