Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer

Nie, Tina; Blair, Hannah A.

doi:10.1007/s11523-023-00971-9

Cited by 5 publications

(2 citation statements)

References 22 publications

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“…In this context, results from the TUXEDO-1 trial evaluating trastuzumab deruxtecan, an antibody-drug conjugate with significant extracranial activity, observed an intracranial response rate of 73.3% in patients with active brain metastases [ 54 ]. In addition, trastuzumab deruxtecan has shown efficacy in patients with HER2-positive metastatic BC who had progressed after prior therapies, including T-DM1 [ 55 ]. These findings suggest that antibody-drug conjugates may have relevant clinical activity in brain metastases, possibly due to an altered blood-brain barrier at the site of metastases.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous Trastuzumab: An Observational Study of Safety and Tolerability in Patients With Early HER2‐Positive Breast Cancer

Otoya,

Valdiviezo,

Morante

et al. 2024

International Journal of Breast Cancer

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Purpose: In Peru, breast cancer (BC) stands as the most predominant malignancy neoplasm among women. Trastuzumab has marked a significant milestone in the management of this disease. It has been shown to improve prognosis in human epidermal growth factor receptor 2 (HER2)–expressing female patients, but its repercussions and efficacy are yet to be analyzed in a context with limited resources.Methods: The study population is made of woman patients aged 18 years and older diagnosed with HER2‐positive BC at Instituto Nacional de Enfermedades Neoplásicas (INEN, Lima, Peru) during 2019–2021 and treated with at least one dose of subcutaneous trastuzumab. We reviewed medical records to register treatment characteristics, adverse events (AEs), disease progression, and survival status. We considered a median follow‐up time of 36 and 45 months for progression and survival status.Results: The majority of patients were over 50 years old (54.29%). Tumor size averaged 19.7 ± 16.1 mm. Lymph nodes were present in 44.78% of patients. Most patients received adjuvant chemotherapy (63.8%) as first‐line treatment. Descriptive analyses of treatment outcomes revealed a 30% toxicity rate, primarily attributed to arthralgia (47.62%), followed by diarrhea, fatigue, and injection site reactions, with relatively lower discontinuation rates compared to larger scale studies. Differences in demographic, clinical, and treatment characteristics were not statistically significant concerning the emergence of AEs (p > 0.05). Progression appeared in nine patients, and the overall survival (OS) rate stood at 98.6% and 92.8%, respectively, during a median follow‐up of 36 and 45 months.Conclusion: The research suggests that subcutaneous trastuzumab is comparable in effectiveness and safety to the intravenous administration. Regional‐specific studies may provide valuable insights into demographic factors influencing treatment outcomes in Peru or other countries. Furthermore, it could represent a more accessible alternative, potentially enhancing patient adherence and optimizing healthcare resource logistics.

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Section: Discussionmentioning

confidence: 99%

Subcutaneous Trastuzumab: An Observational Study of Safety and Tolerability in Patients With Early HER2‐Positive Breast Cancer

Otoya,

Valdiviezo,

Morante

et al. 2024

International Journal of Breast Cancer

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“…Therapy with the monoclonal antibody trastuzumab or trastuzumab-based antibody drug conjugates has an acceptable safety profile in breast, gastric, and colorectal cancers and constitutes a standardof-care. [19][20][21][22] The success and relative safety of these HER2 antibodies spawned interest in developing HER2 CAR T therapy and more than 10 clinical trials ( www. clinicaltrials.…”

Section: What This Study Addsmentioning

confidence: 99%

Systemically administered low-affinity HER2 CAR T cells mediate antitumor efficacy without toxicity

Shabaneh,

Stevens,

Stull

et al. 2024

J Immunother Cancer

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BackgroundThe paucity of tumor-specific targets for chimeric antigen receptor (CAR) T-cell therapy of solid tumors necessitates careful preclinical evaluation of the therapeutic window for candidate antigens. Human epidermal growth factor receptor 2 (HER2) is an attractive candidate for CAR T-cell therapy in humans but has the potential for eliciting on-target off-tumor toxicity. We developed an immunocompetent tumor model of CAR T-cell therapy targeting murine HER2 (mHER2) and examined the effect of CAR affinity, T-cell dose, and lymphodepletion on safety and efficacy.MethodsAntibodies specific for mHER2 were generated, screened for affinity and specificity, tested for immunohistochemical staining of HER2 on normal tissues, and used for HER2-targeted CAR design. CAR candidates were evaluated for T-cell surface expression and the ability to induce T-cell proliferation, cytokine production, and cytotoxicity when transduced T cells were co-cultured with mHER2+ tumor cells in vitro. Safety and efficacy of various HER2 CARs was evaluated in two tumor models and normal non-tumor-bearing mice.ResultsMice express HER2 in the same epithelial tissues as humans, rendering these tissues vulnerable to recognition by systemically administered HER2 CAR T cells. CAR T cells designed with single-chain variable fragment (scFvs) that have high-affinity for HER2 infiltrated and caused toxicity to normal HER2-positive tissues but exhibited poor infiltration into tumors and antitumor activity. In contrast, CAR T cells designed with an scFv with low-affinity for HER2 infiltrated HER2-positive tumors and controlled tumor growth without toxicity. Toxicity mediated by high-affinity CAR T cells was independent of tumor burden and correlated with proliferation of CAR T cells post infusion.ConclusionsOur findings illustrate the disadvantage of high-affinity CARs for targets such as HER2 that are expressed on normal tissues. The use of low-affinity HER2 CARs can safely regress tumors identifying a potential path for therapy of solid tumors that exhibit high levels of HER2.

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Optimizing Solid Tumor Treatment with Antibody–drug Conjugates Using Agent-Based Modeling: Considering the Role of a Carrier Dose and Payload Class

Calopiz,

Linderman,

Thurber

2024

Pharm Res

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Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer

Abstract: This plain language summary represents the opinions of the authors. For a full list of declarations, including funding and author disclosure statements, and copyright information, please see the full text online.

Cited by 5 publications

References 22 publications

Subcutaneous Trastuzumab: An Observational Study of Safety and Tolerability in Patients With Early HER2‐Positive Breast Cancer

Subcutaneous Trastuzumab: An Observational Study of Safety and Tolerability in Patients With Early HER2‐Positive Breast Cancer

Systemically administered low-affinity HER2 CAR T cells mediate antitumor efficacy without toxicity

Optimizing Solid Tumor Treatment with Antibody–drug Conjugates Using Agent-Based Modeling: Considering the Role of a Carrier Dose and Payload Class

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