Current challenges and unmet needs in treating patients with human epidermal growth factor receptor 2-positive advanced breast cancer

Aapro, Matti; Cardoso, Fátima; Curigliano, Giuseppe; Eniu, Alexandru; Gligorov, Joseph; Harbeck, Nadia; Müller, Andreas; Pagani, Olivia; Paluch‐Shimon, Shani; Senkus, Elżbieta; Thürlimann, Beat; Zaman, Khalil

doi:10.1016/j.breast.2022.07.011

Cited by 6 publications

(2 citation statements)

References 92 publications

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“…Systemic treatment in our cohort reflects the actual standard of care using Pertuzumab and Trastuzumab plus docetaxel as first-line treatment, Trastuzumab emtansine (T-DM1) as the second-line treatment, and lapatinib and capecitabine or tucatinib, Trastuzumab and capecitabine as third-line treatment [46].…”

Section: Discussionmentioning

confidence: 99%

Therapies beyond Physiological Barriers and Drug Resistance: A Pilot Study and Review of the Literature Investigating If Intrathecal Trastuzumab and New Treatment Options Can Improve Oncologic Outcomes in Leptomeningeal Metastases from HER2-Positive Breast Cancer

Trifănescu

Mitrea

Galeş

et al. 2023

Cancers

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Leptomeningeal metastases (LM) are a rare but rapidly fatal complication defined by the spread of tumor cells within the leptomeninges and the subarachnoid space, found in approximately 10% of patients with HER2-positive breast cancers. This pilot study evaluated the efficacy of local treatment with intrathecal Trastuzumab (IT) added to systemic treatment. The oncologic outcome of 14 patients with HER2-positive LM is reported. Seven received IT, and seven received standard of care (SOC). The mean number of IT cycles administered was 12.14 ± 4.00. The response rate to CNS after IT treatment + SOC was 71.4%, and three patients (42.8%) obtained durable responses lasting more than 12 months. The median progression-free survival (mPFS) after LM diagnosis was six months, and the median overall survival (mOS) was ten months. The mean values of the PFS in favor of IT therapy (10.6 mo vs. 6.6 mo) and OS (13.7 vs. 9.3 mo) suggest a non-negligible investigation direction in the sense of exploiting intrathecal administration as a possible treatment modality in these patients. Adverse events reported were local pain related to intrathecal administration and one case of arachnoiditis, hematoma, and CSF fistulae. Intrathecal administration of Trastuzumab, alongside systemic treatment and radiotherapy, might improve oncologic outcomes in LM HER2-positive breast cancer with manageable toxicity.

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Section: Discussionmentioning

confidence: 99%

Therapies beyond Physiological Barriers and Drug Resistance: A Pilot Study and Review of the Literature Investigating If Intrathecal Trastuzumab and New Treatment Options Can Improve Oncologic Outcomes in Leptomeningeal Metastases from HER2-Positive Breast Cancer

Trifănescu

Mitrea

Galeş

et al. 2023

Cancers

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“…When small molecule TKIs resistance, we can use mAb combined with small molecule TKI, or an antibody-drug conjugates (ADCs) to reverse HER2 resistance. However then due to the availability and price of ADCs, patients may not use them (4)(5)(6). Therefore, new strategies are needed to reverse HER2 resistance.…”

Section: Introductionmentioning

confidence: 99%

The reversal of anti-HER2 resistance in advanced HER2-positive breast cancer using apatinib: two cases reports and literature review

He¹,

Shen²,

Liu³

et al. 2022

Transl Cancer Res TCR

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Background: Human epidermal growth factor receptor 2 (HER2)-targeted treatment has yielded a notable clinical benefit in patients with HER2-positive breast cancer. However, nearly 50% of patients still suffer disease progression due to resistance to HER2-targeted therapy. After the failure of macromolecular monoclonal antibodies (mAbs) therapy, we can choose small molecule tyrosine kinase inhibitors (TKIs) to reverse HER2 resistance. When small molecule TKIs resistance, we can use mAb combined with small molecule TKI, or antibody-drug conjugates (ADCs) to reverse HER2 resistance. However, then due to the availability and price of ADCs, patients may not use them. Consequently, new therapeutic approaches are required to overcome HER2-targeted therapy resistance. Vascular endothelial growth factor and its receptors (VEGF/VEGFRs) promote tumor angiogenesis. They can also activate downstream signaling pathways to promote tumorigenesis. VEGFR is a key regulator of the tyrosine kinase signaling pathway and may be a potential target in HER2-positive breast cancer. Apatinib is a small molecule TKI that specifically binds to VEGFR2 and thus exerts an antitumor effect. Although there is no definite indication for apatinib in breast cancer, it has a good benefit in advanced gastric cancer. Case Description:The two patients we reported were both HER2-positive breast cancer who we followed for more than 10 years. After the failure of multi-line anti-HER2 treatment, apatinib combined with anti-HER2 treatment had PFS of 8.4 months and 10.6 months, respectively. One patient had grade 2 hand-foot syndrome. The other had grade 2 leukopenia and grade 2 thrombocytopenia, both of them improved after control. And the best response of them were PR and SD, respectively.Conclusions: Our cases demonstrate that, in HER2-positive breast cancer patients with HER2-targeted resistance, apatinib may be able to reverse HER2 resistance. These two cases suggest an alternative method for clinical HER2-targeted treatment of drug-resistant breast cancer patients and provide new insights for future research.

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Trastuzumab-Deruxtecan: Redefining HER2 as a Tumor Agnostic Biomarker

Zouein,

Karam,

Strickler

et al. 2024

Targ Oncol

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Current challenges and unmet needs in treating patients with human epidermal growth factor receptor 2-positive advanced breast cancer

Cited by 6 publications

References 92 publications

Therapies beyond Physiological Barriers and Drug Resistance: A Pilot Study and Review of the Literature Investigating If Intrathecal Trastuzumab and New Treatment Options Can Improve Oncologic Outcomes in Leptomeningeal Metastases from HER2-Positive Breast Cancer

Therapies beyond Physiological Barriers and Drug Resistance: A Pilot Study and Review of the Literature Investigating If Intrathecal Trastuzumab and New Treatment Options Can Improve Oncologic Outcomes in Leptomeningeal Metastases from HER2-Positive Breast Cancer

The reversal of anti-HER2 resistance in advanced HER2-positive breast cancer using apatinib: two cases reports and literature review

Trastuzumab-Deruxtecan: Redefining HER2 as a Tumor Agnostic Biomarker

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