Sacituzumab govitecan: antibody-drug conjugate in triple-negative breast cancer and other solid tumors

Fenn, Kathleen; Kalinsky, Kevin

doi:10.1358/dot.2019.55.9.3039669

Cited by 39 publications

(28 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Trop-2 expression is detected in all BC subtypes and membrane localization has been associated with poor prognosis. 20 , 21 , 22 , 23 , 24 …”

Section: Resultsmentioning

confidence: 99%

“…Trop-2 expression is detected in all BC subtypes and membrane localization has been associated with poor prognosis. [20][21][22][23][24] SG (IMMU-132, Trodelvy®) is a first-in-class anti-Trop-2 ADC. It consists of the humanized mAb (hRS7) and SN-38 as cytotoxic payload (SN-38), which is the active metabolite of irinotecan (CPT-11) and functions as a topoisomerase I inhibitor.…”

Section: Sacituzumab Govitecanmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

“…Trop-2 expression is detected in all BC subtypes and membrane localization has been associated with poor prognosis. 20 , 21 , 22 , 23 , 24 …”

Section: Resultsmentioning

confidence: 99%

Section: Sacituzumab Govitecanmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Sacituzumab govitecan is a novel antibody-drug conjugate (ADC). It is composed of a humanized monoclonal antibody that is connected to a modified active metabolite of irinotecan, SN-38 ( Bardia et al, 2017 ; Fenn & Kalinsky, 2019 ). Modification of SN-38 allows for it to be less active from under physiologic conditions and prevents cross-reactivity during transport in the serum.…”

Section: Pharmacology and Mechanism Of Actionmentioning

confidence: 99%

“…SN-38 is released into the cell via pH-mediated release, where it functions as a topoisomerase-I (topo-I) inhibitor. It stabilizes the complex between topo-I and DNA, which eventually leads to double-stranded DNA breakage ( Cardillo et al, 2015 ; Fenn & Kalinsky, 2019 ; Goldenberg et al, 2015 ; Govindan et al, 2012 ; Voigt et al, 1998 ). This then causes upregulation of proapoptotic protein signals p53 and p21, ultimately causing G1 cell cycle arrest and activating the intrinsic apoptotic pathway.…”

Section: Pharmacology and Mechanism Of Actionmentioning

confidence: 99%

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer

Fleming¹,

Karpio²,

Lombardo³

2021

JADPRO

View full text Add to dashboard Cite

Sacituzumab govitecan was initially approved in April 2020 under accelerated approval for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. A confirmatory phase III trial evaluating sacituzumab govitecan vs. chemotherapy of the provider’s choice was published in April 2021. Based on this trial, the FDA granted sacituzumab govitecan full regulatory approval. This antibody-drug conjugate is composed of a monoclonal antibody targeted at Trop-2 and contains the active metabolite of irinotecan, SN-38, as a cytotoxic side moiety. In a phase III clinical trial, sacituzumab govitecan demonstrated a median progression-free survival of 5.7 months vs. 1.7 months with chemotherapy. It is now an additional option for patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

show abstract

“…Sacituzumab govitecan-hziy antibody-drug targeting trophoblast cell surface antigen 2[59] www.videleaf.com…”

mentioning

confidence: 99%

Overview of New Treatments with Immunotherapy for Breast Cancer and a Proposal of a Combination Therapy

Morales¹,

Rodríguez²,

Cruz³

et al. 2021

Prime Archives in Molecular Sciences

View full text Add to dashboard Cite

According to data from the U.S. National Cancer Institute, cancer is one of the leading causes of death worldwide with approximately 14 million new cases and 8.2 million cancerrelated deaths in 2018. More than 60% of the new annual cases in the world occur in Africa, Asia, Central America, and South America, with 70% of cancer deaths in these regions. Breast cancer is the most common cancer in women, with 266,120 new cases in American women and an estimated 40,920 deaths for 2018. Approximately one in six women diagnosed with breast cancer will die in the coming years. Recently, novel therapeutic strategies have been implemented in the fight against breast cancer, including molecules able to block signaling pathways, an inhibitor of poly [ADP-ribose] polymerase (PARP), growth receptor blocker antibodies, or those that reactivate the immune system by inhibiting the activities of inhibitory receptors like cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death protein 1 (PD-1). However, novel targets include reactivating the Th1 immune response, changing tumor microenvironment, and co-activation of other components of the Prime Archives in Molecular Sciences: 2 nd Edition 3 www.videleaf.com immune response such as natural killer cells and CD8+ T cells among others. In this article, we review advances in the treatment of breast cancer focused essentially on immunomodulatory drugs in targeted cancer therapy. Based on this knowledge, we formulate a proposal for the implementation of combined therapy using an extracorporeal immune response reactivation model and cytokines plus modulating antibodies for co-activation of the Th1-and natural killer cell (NK)-dependent immune response, either in situ or through autologous cell therapy. The implementation of "combination immunotherapy" is new hope in breast cancer treatment. Therefore, we consider the coordinated activation of each cell of the immune response that would probably produce better outcomes. Although more research is required, the results recently achieved by combination therapy suggest that for most, if not all, cancer patients, this tailored therapy may become a realistic approach in the near future.

show abstract

Sacituzumab govitecan: antibody-drug conjugate in triple-negative breast cancer and other solid tumors

Cited by 39 publications

References 37 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

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer

Overview of New Treatments with Immunotherapy for Breast Cancer and a Proposal of a Combination Therapy

Contact Info

Product

Resources

About