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Article: Lessons from recent trials of antibody-drug conjugates in breast cancer.

Tarantino, Paolo

Clinical advances in hematology & oncology : H&O

2022 Volume 20, Issue 12, Page(s) 719–722

MeSH term(s)	Humans ; Female ; Immunoconjugates/therapeutic use ; Breast Neoplasms/drug therapy ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Immunological/therapeutic use
Chemical Substances	Immunoconjugates ; Antineoplastic Agents ; Antineoplastic Agents, Immunological
Language	English
Publishing date	2022-12-05
Publishing country	United States
Document type	Interview
ZDB-ID	2271951-9
ISSN	1543-0790
ISSN	1543-0790
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Zs.A 6505: Show issues

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Article ; Online: Detecting and Managing T-DXd-Related Interstitial Lung Disease: The Five "S" Rules.

Tarantino, Paolo / Tolaney, Sara M

JCO oncology practice

2023 Volume 19, Issue 8, Page(s) 526–527

Abstract: Media: see text]. ...

Abstract	[Media: see text].
MeSH term(s)	Humans ; Lung Diseases, Interstitial/chemically induced ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/therapy
Language	English
Publishing date	2023-05-19
Publishing country	United States
Document type	Editorial ; Video-Audio Media ; Comment
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.23.00097
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Zs.A 7198: Show issues

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Article ; Online: The Dawn of the Antibody-Drug Conjugates Era: How T-DM1 Reinvented the Future of Chemotherapy for Solid Tumors.

Tarantino, Paolo / Tolaney, Sara M

Cancer research

2022 Volume 82, Issue 20, Page(s) 3659–3661

Abstract: Delivering targeted chemotherapy through antibody-drug conjugates (ADC) has emerged as an extremely effective therapeutic strategy for multiple types of cancer. The first agent of this class to be established for treating a solid tumor was trastuzumab ... ...

Abstract	Delivering targeted chemotherapy through antibody-drug conjugates (ADC) has emerged as an extremely effective therapeutic strategy for multiple types of cancer. The first agent of this class to be established for treating a solid tumor was trastuzumab emtansine (T-DM1), approved in 2013 for the treatment of HER2-positive metastatic breast cancer. Much of the knowledge that led to this approval came from the landmark Cancer Research publication by Lewis Phillips and colleagues in 2008, where they described the in vitro and in vivo efficacy, pharmacokinetics, and toxicity of T-DM1, demonstrating its relevant preclinical activity against HER2-positive breast cancer models. In this article, the authors also explored the use of different linkers to conjugate the cytotoxic payload to the trastuzumab vehicle, demonstrating improved stability, efficacy, and tolerability of the compound when adopting a specific thioether linker. The findings from this work not only set the stage for the clinical development of T-DM1, but also highlighted the modularity of ADCs, with small changes in their components able to dramatically impact their activity and toxicity. This finding would prove key for the development of novel ADCs, several of which are now reshaping the way we treat breast cancer and other cancer types. In this commentary, we discuss the key implications of the work by Phillips and colleagues, putting it in context of the current and anticipated expansion in the use of ADCs to treat cancer. See related article by Phillips et al., Cancer Res 2008;68:9280-90.
MeSH term(s)	Ado-Trastuzumab Emtansine ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Immunoconjugates/therapeutic use ; Maytansine/therapeutic use ; Sulfides ; Trastuzumab/therapeutic use
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Immunoconjugates ; Sulfides ; Maytansine (14083FR882) ; Trastuzumab (P188ANX8CK) ; Ado-Trastuzumab Emtansine (SE2KH7T06F)
Language	English
Publishing date	2022-09-20
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-22-2324
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Uh III Zs.135/5: Show issues

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Article ; Online: The American Society of Clinical Oncology-College of American Pathologists Guideline Update for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer.

Schnitt, Stuart J / Tarantino, Paolo / Collins, Laura C

Archives of pathology & laboratory medicine

2023 Volume 147, Issue 9, Page(s) 991–992

MeSH term(s)	Humans ; Female ; Breast Neoplasms/diagnosis ; Breast Neoplasms/metabolism ; Pathologists ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Medical Oncology
Chemical Substances	ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Biomarkers, Tumor
Language	English
Publishing date	2023-06-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2023-0187-ED
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Ud II Zs.36: Show issues

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Article ; Online: HER2-low expression in breast oncology: treatment implications in the smart chemotherapy era.

Giugliano, Federica / Curigliano, Giuseppe / Tarantino, Paolo

European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)

2023 Volume 32, Issue 2, Page(s) 149–154

Abstract: Human epidermal growth factor 2 (HER2)-low breast cancers, defined as tumors exhibiting a HER2 IHC score of 1+ or 2+ nonamplified, represent an emerging targetable entity in the clinicopathologic landscape of breast cancer. Traditionally considered as ... ...

Abstract	Human epidermal growth factor 2 (HER2)-low breast cancers, defined as tumors exhibiting a HER2 IHC score of 1+ or 2+ nonamplified, represent an emerging targetable entity in the clinicopathologic landscape of breast cancer. Traditionally considered as not sensitive to HER2-targeting agents, these tumors have shown to be susceptible to a new class of drugs, namely antibody-drug conjugates (ADCs). Indeed, the DESTINY-Breast04 phase 3 trial demonstrated the remarkable activity of trastuzumab deruxtecan for treating both hormone-receptor (HR)-positive and triple-negative metastatic breast cancers that show HER2-low expression, reshaping treatment algorithms for these diseases. Concomitantly, the TROPiCS-02 and the ASCENT phase 3 trials have established the role of the anti-Trop-2 ADC sacituzumab govitecan for HR-positive and triple-negative breast cancer, respectively. A careful evaluation of these trials, with their inclusion/exclusion criteria, efficacy and toxicity results, is required in order to understand how best to treat HER2-low metastatic breast cancer in the context of a rapidly evolving therapeutic landscape. The purpose of this narrative review is to recapitulate the available evidence on the use of ADCs in the treatment of HER2-low breast cancer, providing a perspective on their current role in clinical practice.
MeSH term(s)	Humans ; Female ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/pathology ; Receptor, ErbB-2
Chemical Substances	Antineoplastic Agents ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2023-01-17
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1137033-6
ISSN	1473-5709 ; 0959-8278
ISSN (online)	1473-5709
ISSN	0959-8278
DOI	10.1097/CEJ.0000000000000781
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Zs.A 3621: Show issues

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Article ; Online: How I treat HER2-low advanced breast cancer.

Schlam, Ilana / Tolaney, Sara M / Tarantino, Paolo

Breast (Edinburgh, Scotland)

2023 Volume 67, Page(s) 116–123

Abstract: Introduction: Targeting low levels of human receptor epidermal growth factor 2 (HER2) expression has reshaped the treatment paradigm for half of the patients with advanced breast cancer. HER2-low is currently defined as a HER2 immunohistochemical ... ...

Abstract	Introduction: Targeting low levels of human receptor epidermal growth factor 2 (HER2) expression has reshaped the treatment paradigm for half of the patients with advanced breast cancer. HER2-low is currently defined as a HER2 immunohistochemical expression of 1+ or 2+ without amplification by in-situ hybridization. Until recently, HER2-targeted agents were ineffective in treating patients with HER2-low disease. Areas covered: In this narrative review, we summarize the current management of HER2-low breast cancer. We highlight the findings of the DESTINY-Breast 04 phase 3 trial, which confirmed the efficacy of trastuzumab-deruxtecan (T-DXd) for the treatment of patients with advanced, pretreated HER2-low breast cancer. We also discuss how to implement this new treatment option in treatment algorithms of hormone receptor (HR)-positive and triple-negative tumors, as well as how to optimally manage selected toxicities of T-DXd. Expert opinion: T-DXd is currently the standard of care for patients with advanced, pretreated, HER2-low breast cancer. Based on the design of the DESTINY-Breast04 trial, the current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer. Up to 10-15% of the patients receiving T-DXd are expected to develop interstitial lung disease, which in 1-2% of the cases can be fatal. Adequate monitoring and prompt management are required to minimize the impact of ILD and to safely implement T-DXd in clinical practice.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/pathology ; Receptor, ErbB-2/metabolism ; Trastuzumab ; Antineoplastic Agents/therapeutic use
Chemical Substances	Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK) ; Antineoplastic Agents
Language	English
Publishing date	2023-01-12
Publishing country	Netherlands
Document type	Review ; Journal Article
ZDB-ID	1143210-x
ISSN	1532-3080 ; 0960-9776
ISSN (online)	1532-3080
ISSN	0960-9776
DOI	10.1016/j.breast.2023.01.005
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Zs.A 3620: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 588: Show issues

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Article ; Online: Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles.

Fenton, Mary Anne / Tarantino, Paolo / Graff, Stephanie L

Current oncology (Toronto, Ont.)

2023 Volume 30, Issue 12, Page(s) 10211–10223

Abstract: Antibody drug conjugates (ADCs) have emerged as a highly effective treatment strategy across breast cancer (BC) subtypes, including human epidermal growth factor receptor 2-positive (HER2+), hormone-receptor positive (ER/PR+), and triple-negative breast ... ...

Abstract	Antibody drug conjugates (ADCs) have emerged as a highly effective treatment strategy across breast cancer (BC) subtypes, including human epidermal growth factor receptor 2-positive (HER2+), hormone-receptor positive (ER/PR+), and triple-negative breast cancer (TNBC). Over the past twenty years, ADCs have undergone relevant evolutions, from target diversity to payload ratio, to linker design, allowing for a progressive increase in their efficacy. From the first-generation ADC, trastuzumab emtansine (T-DM1), approved in 2013 for HER2+ breast cancer, to next generation ADCs such as sacituzumab govitecan and trastuzumab deruxtecan, to emerging ADCs on the horizon, we continue to see unparalleled efficacy compared to traditional chemotherapy. However, each ADC has brought a new cadre of adverse events for clinicians and patients to manage. Importantly, with the development and approval of several ADCs to treat metastatic breast cancer, there are unanswered clinical questions surrounding how to optimally sequence treatment for patients who may be candidates for more than one ADC and, in general, how to treat patients beyond progression on ADCs. From bench to bedside, in this review, we will discuss the pharmacology and current indications for the novel ADCs trastuzumab deruxtecan and sacituzumab govitecan. Highlighting emerging ADCs and ongoing clinical trials, we will anticipate the changes in the breast cancer treatment paradigm. Lastly, we will outline the available data and current approaches for adverse event management and sequencing strategies for ADCs in clinical practice, including proposed mechanisms of resistance.
MeSH term(s)	Humans ; Ado-Trastuzumab Emtansine ; Triple Negative Breast Neoplasms ; Immunoconjugates/therapeutic use
Chemical Substances	Ado-Trastuzumab Emtansine (SE2KH7T06F) ; Immunoconjugates
Language	English
Publishing date	2023-11-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol30120743
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Zs.A 4305: Show issues

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Article ; Online: Managing adverse events of sacituzumab govitecan.

Schlam, Ilana / Tarantino, Paolo / Tolaney, Sara M

Expert opinion on biological therapy

2023 Volume 23, Issue 11, Page(s) 1103–1111

Abstract: Introduction: The development of antibody-drug conjugates (ADCs) have revolutionized treatment for breast cancer. Sacituzumab govitecan (SG), a Trop2-targeted ADC, has demonstrated remarkable efficacy in triple-negative breast cancer (TNBC) and hormone ... ...

Abstract	Introduction: The development of antibody-drug conjugates (ADCs) have revolutionized treatment for breast cancer. Sacituzumab govitecan (SG), a Trop2-targeted ADC, has demonstrated remarkable efficacy in triple-negative breast cancer (TNBC) and hormone receptor-positive metastatic breast cancer. Areas covered: We summarize the evidence for SG use in the treatment of metastatic breast cancer, discuss the toxicity profile, and present strategies to manage adverse events. Expert opinion: Hematologic toxicities are frequently observed with SG therapy. Neutropenia, reported in up to 72% of cases, often requires dose reductions or delays. Granulocyte colony-stimulating factor can be helpful in managing and preventing this toxicity. Anemia is another common toxicity and patients may require transfusions of packed red blood cells. Gastrointestinal toxicities are also common. A tailored regimen of prophylactic antiemetics (2-3 agents) should be initiated before SG infusion. For diarrhea, infectious workup should be considered on a case-by-case basis; patients should start loperamide and fluid/electrolyte replacement if necessary. Severe diarrhea associated with cholinergic syndrome should prompt the administration of atropine. Fatigue occurs in approximately half of the patients receiving SG, and <50% of patients experience complete alopecia during treatment. The approval of SG has significantly improved treatment outcomes; however, effective management of the toxicities is critical to optimize patient care and treatment adherence.
MeSH term(s)	Humans ; Antigens, Neoplasm ; Camptothecin/therapeutic use ; Immunoconjugates/therapeutic use ; Triple Negative Breast Neoplasms/drug therapy ; Diarrhea/chemically induced ; Diarrhea/drug therapy
Chemical Substances	sacituzumab govitecan (M9BYU8XDQ6) ; Antigens, Neoplasm ; Camptothecin (XT3Z54Z28A) ; Immunoconjugates
Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1080/14712598.2023.2267975
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Zs.A 6094: Show issues

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Article ; Online: The efficacy of trastuzumab-deruxtecan for the treatment of patients with advanced HER2-low breast cancer.

Schlam, Ilana / Tolaney, Sara M / Tarantino, Paolo

Expert review of anticancer therapy

2023 , Page(s) 1–8

Abstract: Introduction: Until recently, the available human receptor epidermal growth factor 2 (HER2) targeted agents were ineffective for treating patients with HER2-low expressing breast cancer (defined as immunohistochemical expression of 1+ or 2+ without ... ...

Abstract	Introduction: Until recently, the available human receptor epidermal growth factor 2 (HER2) targeted agents were ineffective for treating patients with HER2-low expressing breast cancer (defined as immunohistochemical expression of 1+ or 2+ without amplification). The development of novel and potent HER2-directed antibody-drug conjugates, affective at treating HER2-low expressing breast cancers, have changed the way we think about HER2-low expression and expanded the treatment options for many patients with advanced disease. Areas covered: In this review, we summarize the current management of HER2-low breast cancer and commonly encountered challenges such as treatment sequencing and toxicity management. Expert opinion: trastuzumab deruxtecan (T-DXd) is a treatment option for patients with advanced, HER2-low breast cancer, irrespective of the hormone receptor status. The current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer; however, other agents are available in this setting and risks and benefits for each should be considered in shared decision making. Up to 10-15% of patients receiving T-DXd develop interstitial lung disease. Patient and clinician education are key to safely implement T-DXd in clinical practice.
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2112544-2
ISSN	1744-8328 ; 1473-7140
ISSN (online)	1744-8328
ISSN	1473-7140
DOI	10.1080/14737140.2023.2171993
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Zs.A 5907: Show issues

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Article ; Online: Atezolizumab and Bevacizumab in Hepatocellular Carcinoma.

Tarantino, Paolo / Curigliano, Giuseppe

The New England journal of medicine

2021 Volume 383, Issue 7, Page(s) 694–695

MeSH term(s)	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Carcinoma, Hepatocellular ; Humans ; Liver Neoplasms
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Bevacizumab (2S9ZZM9Q9V) ; atezolizumab (52CMI0WC3Y)
Language	English
Publishing date	2021-06-18
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2021840
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