Targeting HER2 in Breast Cancer: Latest Developments on Treatment Sequencing and the Introduction of Biosimilars

Tesch, Megan E.; Gelmon, Karen A.

doi:10.1007/s40265-020-01411-y

Cited by 30 publications

(27 citation statements)

References 171 publications

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“…46 This accelerated approval was based on the results of the DESTINY-Breast01 trial that showed impressive antitumor activity of T-DXd in heavily pretreated patients. 18 , 47 In January 2021, T-DXd received a conditional marketing authorization by the EMA for HER2+ BC after two or more prior anti-HER2-based regimens. 48 , 49 A timeline of development and regulatory milestones of T-DXd in BC is shown in Figure 1 B.…”

Section: Resultsmentioning

confidence: 99%

Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody–drug conjugates in the breast cancer treatment landscape

et al. 2021

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Background: Two new antibodyedrug conjugates (ADCs) containing a topoisomerase I inhibitor payload have recently emerged in the breast cancer (BC) treatment landscape. Sacituzumab govitecan-hziy (SG) is a first-in-class antitrophoblast cell-surface antigen 2 ADC approved for pretreated metastatic triple-negative breast cancer (mTNBC) and trastuzumab deruxtecan (T-DXd) gained approval for human epidermal growth factor receptor-2 (HER2)-positive advanced BC (aBC). We aim to provide a contemporary review and the current clinical trial landscape of SG and T-DXd in BC. Materials and methods: We conducted a literature search from Medline database through PubMed, major conference proceedings [abstracts from European Society for Medical Oncology (Breast) Congress, American Society of Clinical Oncology annual meeting, San Antonio Breast Cancer Symposium] and ClinicalTrials.gov with search terms 'sacituzumab govitecan', 'IMMU-132', 'trastuzumab deruxtecan' and 'DS-8201a' up to 21 March 2021. Results: We assessed 293 records for eligibility, of which 153 were included in this review after screening and exclusion. For SG, efficacy and safety data are available from a phase III trial in pretreated mTNBC and from a phase I/II basket study in mTNBC and hormone receptor-positive/HER2-negative aBC. Thirteen trials with pending primary analysis are ongoing with SG as single agent or in combination, of which 11 are enrolling (2/11 in the early setting). For T-DXd, efficacy/safety data are available as single agent in pretreated HER2-positive (phase Ib and phase II) and in HER2low aBC (phase Ib), and in combination with nivolumab in HER2-low/positive aBC (phase Ib). Of 23 ongoing trials with T-DXd, 12 are open for enrollment and 3 phase III trials have completed recruitment. The distinct safety profiles of both drugs and their management are discussed. Conclusion: Given their robust single-agent activity, SG and T-DXd are expected to substantially impact treatment standards, both in and far beyond the currently approved indications. Several trials are investigating new treatment settings for both drugs, including a transition to earlier lines and combinations with other anticancer treatments such as immune checkpoint inhibitors.

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Section: Resultsmentioning

confidence: 99%

Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody–drug conjugates in the breast cancer treatment landscape

et al. 2021

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“…HER2 overexpression is a strong predictive factor for response to anti-HER2 therapies, which target different regions of the HER2 protein [ 16 ]. T-DXd is a monoclonal antibody-drug conjugate (ATC code: L01XC41).…”

Section: Her2 Targeting By T-dxd: Preclinical Studiesmentioning

confidence: 99%

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors

Indini

Rijavec

Grossi

2021

IJMS

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HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors.

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“…[31][32][33] Bunla birlikte alternatif olarak firmalar biyobenzer ilaç geliştirme çalışmalarını hızlandırmışlardır.34 Meme kanseri için insan epidermal büyüme faktörü reseptörü 2 (HER2) pozitifliği yüksek dereceli histoloji, lenf nodu tutulumu, daha yüksek hastalık nüksetmesi ve mortalite oranları ile ilişkisi nedeniyle kötü prognoz çerçevesi oluşturmaktadır.3 5 Meme kanserine karşı bir monoklonal antikor olan trastuzumab (Herceptin Roche / Genentech GmbH), bu hastalığın doğal seyrini değiştiren ve HER2 proteinini hedefleyen etkili bir ilaçtır. 5,35,36 Trastuzumab biyobenzerinin yanı sıra tedavide, tümör anjiyogenezini bloke edebilen bevacizumab(vasküler endotelyal büyüme faktörünü bağlayan bir monoklonal antikor -VEGF)da kulanılmaktadır. 24,32 Günümüzde, mAb'lerden trastuzumab ve pertuzumab dahil olmak üzere birçok anti-HER 2 ajanı klinik olarak kullanılmaktadır.…”

Section: Biyobenzerlerin öNemiunclassified

“…Trastuzumab insan epidermal büyüme faktörü reseptörü 2 (HER2) -pozitif metastatik meme kanseri için bir monoterapi, kemoterapi veya hormon tedavisi ile birlikte kullanılabilir. 17,35 Bunlarla birlikte FDA ve EMA tarıfından onaylanan trastuzumab biyobenzerleri hastalık tedavisini daha erişilebilir bir hale getirmişlerdir. 35 Meme kanseri tedavisi, ek tedavi veya tedaviyle ilişkili yan etkilerin önlenmesinde belirtilen günümüzde kullanılmakta olan EMA ve FDA'den 2018'e kadar onaylı biyobenzerlerleri Tablo 3. de verilmektedir.…”

Section: Biyobenzerlerin öNemiunclassified

“…17,35 Bunlarla birlikte FDA ve EMA tarıfından onaylanan trastuzumab biyobenzerleri hastalık tedavisini daha erişilebilir bir hale getirmişlerdir. 35 Meme kanseri tedavisi, ek tedavi veya tedaviyle ilişkili yan etkilerin önlenmesinde belirtilen günümüzde kullanılmakta olan EMA ve FDA'den 2018'e kadar onaylı biyobenzerlerleri Tablo 3. de verilmektedir. 32,37 Trastuzumab biyobenzerinin referans ürününe benzeyen biyobenzerliğini göstermek için gereken karşılaştırılabilirlik alıştırmasının aşamalı süreci ise Şekil 2. de görülmektedir.…”

Section: Biyobenzerlerin öNemiunclassified

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et al. 2021

Beykent Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi

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Biyobenzer ilaçlar, saflık, güvenlik ve etkinlik açısından referans kaynağından klinik olarak anlamlı farklılıklara sahip olmayan lisanslı biyolojiklere (referans biyolojikler) oldukça benzer olduğu gösterilen biyolojikler olarak tanımlanmaktadır. Biyobenzerler, biyolojik kaynaklı ilaçlarla tedavisi olan hastalıklar açısından alternatif ilaçlar olarak üretilmektedir. Bu sayede kanser gibi spesifik hastalıklara yönelik tedaviler çeşitlilik kazanmaktadır. Örneğin meme kanseri için kullanılan biyobenzerler geliştirildikçe gelecekte bu hastalığın tedavilerine erişilebilirlik artacaktır ve bu gelişmeler de anti-HER2 ve anti-VEGF tedavisinin daha yaygın kullanımına olanak sağlayacaktır. Meme kanseri tedavisinde kullanılan Trastuzumab için, Avrupa patenti 2014'te, ABD patenti 2019'da sona ermiştir. Patent sürelerinin dolması bu biyobenzer ilaçların geliştirilmesini hızlandırmıştır. Bu derlemede öncelikle biyobenzerler hakkında genel bilgiler aktarılmış ve Göğüs/Meme kanseri için kullanılan biyobenzerler hakkında ayrıntılı tartışma gerçekleştirilmiştir.

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Targeting HER2 in Breast Cancer: Latest Developments on Treatment Sequencing and the Introduction of Biosimilars

Cited by 30 publications

References 171 publications

Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody–drug conjugates in the breast cancer treatment landscape

Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody–drug conjugates in the breast cancer treatment landscape

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors

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