scholarly journals Novel antibody–drug conjugates for triple negative breast cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592091598 ◽  
Author(s):  
Aiko Nagayama ◽  
Neelima Vidula ◽  
Leif Ellisen ◽  
Aditya Bardia

Triple negative breast cancer (TNBC) is a heterogenous subtype of breast cancer often associated with an aggressive phenotype and poor prognosis. Antibody–drug conjugate (ADC), comprising of a monoclonal antibody linked to a cytotoxic payload by a linker, is gaining increasing traction as an anti-cancer therapeutic. Emerging ADC drugs such as sacituzumab govitecan (IMMU-132) and trastuzumab deruxtecan (DS-8201a) are in late stages of clinical development for patients with metastatic breast cancer, including TNBC. In this article, we review and discuss the development and clinical application of ADCs in patients with advanced TNBC.

2020 ◽  
pp. 106002802096654
Author(s):  
John M. Seligson ◽  
Alexandra M. Patron ◽  
Michael J. Berger ◽  
R. Donald Harvey ◽  
Nathan D. Seligson

Objective: To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease. Data Sources: A literature search was conducted utilizing PubMed and MEDLINE databases, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and September 3, 2020. Keywords included sacituzumab govitecan (-hziy), IMMU-132, Trop-2 (trophoblast cell-surface antigen 2), and TACSTD2. Study Selection and Data Extraction: All English-language trials involving sacituzumab govitecan for mTNBC were included and discussed. Data Synthesis: Sacituzumab govitecan is an antibody-drug conjugate targeted for Trop-2 and conjugated to the topoisomerase-1 inhibitor SN-38. It was granted accelerated Food and Drug Administration approval based on a phase I/II single-arm, multicenter study (n = 108), which reported an overall response rate of 33.3% and median duration of response of 7.7 months (95% CI = 4.9-10.8 months). Common adverse reactions include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, abdominal pain, and respiratory infection. A confirmatory, randomized phase III clinical trial is ongoing (NCT02574455). Relevance to Patient Care and Clinical Practice: This review covers the efficacy, safety, and clinical use of sacituzumab govitecan, a third-line drug with activity in mTNBC. Conclusion: Sacituzumab govitecan is a novel targeted treatment with promising activity in mTNBC.


2018 ◽  
Author(s):  
Marc Hillairet de Boisferon ◽  
Caroline Mignard ◽  
Coralie Durix ◽  
Toshimitsu Uenaka ◽  
Katherine Rybinski ◽  
...  

2019 ◽  
Author(s):  
Yingnan Si ◽  
Nghi Dang ◽  
Seulhee Kim ◽  
Lufang Zhou ◽  
Xiaosi Han ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12583-e12583
Author(s):  
Eriko Katsuta ◽  
Li Yan ◽  
Mateusz Opyrchal ◽  
Pawel Kalinski ◽  
Kazuaki Takabe

e12583 Background: Cytotoxic T-lymphocytes (CTLs) infiltration into tumor is a positive prognostic factor in breast cancer. Infiltration of CTLs are believed to be driven by mutation-induced neoantigens, thus, higher tumor mutation burden (TMB) is considered an important predictor of tumor immunogenicity and response to immunotherapy, but the association between intratumoral CTL counts and TMB in the overall cancer prognosis remains unclear. Methods: Utilizing publicly available breast cancer cohorts, we established Functional Hotness Score (FHS), based on CD8A, GZMB and CXCL10 gene expression levels of bulk tumors. The associations of FHS and breast cancer patient prognosis as well as distinct immunity markers were analyzed. Results: Breast cancer patients with high-FHS tumors demonstrated significantly better survival. FHS was lower in metastatic breast cancer. Among breast cancer subtypes, triple-negative breast cancer (TNBC) showed the highest FHS. FHS predicted patient survival not in hormone receptor (HR)-positive but in HR-negative, especially TNBCs. The high-FHS TNBCs enhanced not only CD8+ T cell infiltration, but also a broader type-1 anti-cancer immunity. The patients with the high-FHS patients showed better prognosis not only in high-TMB tumors but also in low-TMB TNBCs. The combination of high-TMB with high-FHS identified the unique subset of patients who did not recur over time. Conclusions: In conclusion, TNBCs with high-FHS based on the expression levels of CD8A, GZMB and CXCL10 showed improved prognosis with higher anti-cancer immunity regardless of TMB, and constituting an independent prognostic marker of survival, particularly robust when combined with TMB.


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