A New Kid on the Block: Sacituzumab Govitecan for the Treatment of Breast Cancer and Other Solid Tumors

Human trophoblast cell-surface antigen-2 (Trop-2) is a membrane glycoprotein involved in cell proliferation and motility, frequently overexpressed in epithelial tumors. Thus, it represents an attractive target for anticancer therapies. Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate, consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolyzable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment. Indeed, unprecedented results have been observed with SG in patients with heavily pretreated advanced triple-negative breast cancer and urothelial carcinomas, and the drug has already received approval for these indications. These results are coupled with a manageable toxicity profile, with neutropenia and diarrhea as the most frequent adverse events, mainly of grades 1–2. While several trials are exploring SG activity in different tumor types and settings, potential biomarkers of response are under investigation. Among these, Trop-2 overexpression and the presence of BRCA1/2 mutations seem to be the most promising. We review the available literature concerning SG, with a focus on its toxicity spectrum and possible biomarkers of its response.

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Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer

Annals of Pharmacotherapy ◽

10.1177/1060028020966548 ◽

2020 ◽

pp. 106002802096654

Author(s):

John M. Seligson ◽

Alexandra M. Patron ◽

Michael J. Berger ◽

R. Donald Harvey ◽

Nathan D. Seligson

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

English Language ◽

Triple Negative ◽

Data Extraction ◽

Phase Iii ◽

Antibody Drug Conjugate ◽

Drug Conjugate ◽

Topoisomerase 1 ◽

Antibody Drug

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.

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Faculty Opinions recommendation of Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727407789.793559069 ◽

2019 ◽

Author(s):

Ahmad Awada

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Efficacy And Safety ◽

Antibody Drug Conjugate ◽

Drug Conjugate ◽

Heavily Pretreated ◽

Pretreated Patients ◽

Antibody Drug

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Abstract PD3-14: Phase 1 study of the antibody-drug conjugate SGN-LIV1A in patients with heavily pretreated triple-negative metastatic breast cancer

10.1158/1538-7445.sabcs17-pd3-14 ◽

2018 ◽

Cited By ~ 2

Author(s):

S Modi ◽

L Pusztai ◽

A Forero ◽

M Mita ◽

KD Miller ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Triple Negative ◽

Phase 1 ◽

Metastatic Breast ◽

Antibody Drug Conjugate ◽

Phase 1 Study ◽

Drug Conjugate ◽

Heavily Pretreated ◽

Antibody Drug

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Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2016.70.8297.2017.2.test ◽

2017 ◽

Vol 2017 (2) ◽

pp. 2141-2148 ◽

Cited By ~ 3

Author(s):

Aditya Bardia ◽

Ingrid A. Mayer ◽

Jennifer R. Diamond ◽

Rebecca L. Moroose ◽

Steven J. Isakoff ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Efficacy And Safety ◽

Antibody Drug Conjugate ◽

Drug Conjugate ◽

Heavily Pretreated ◽

Pretreated Patients ◽

Antibody Drug

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Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”): a randomized multicenter study

npj Breast Cancer ◽

10.1038/s41523-021-00244-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Linda T. Vahdat ◽

Peter Schmid ◽

Andres Forero-Torres ◽

Kimberly Blackwell ◽

Melinda L. Telli ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Primary Endpoint ◽

Triple Negative ◽

Progression Free Survival ◽

Antibody Drug Conjugate ◽

Open Label ◽

Common Grade ◽

Open Label Phase ◽

Grade 3

AbstractThe METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.

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Repositioning metformin and propranolol for colorectal and triple negative breast cancers treatment

Scientific Reports ◽

10.1038/s41598-021-87525-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

L. E. Anselmino ◽

M. V. Baglioni ◽

F. Malizia ◽

N. Cesatti Laluce ◽

C. Borini Etichetti ◽

...

Keyword(s):

Breast Cancer ◽

Side Effects ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Drug Repositioning ◽

Combined Treatment ◽

Alternative Therapy ◽

Breast Cancers ◽

Mesenchymal Transition ◽

Tumor Types

AbstractDrug repositioning refers to new uses for existing drugs outside the scope of the original medical indications. This approach fastens the process of drug development allowing finding effective drugs with reduced side effects and lower costs. Colorectal cancer (CRC) is often diagnosed at advanced stages, when the probability of chemotherapy resistance is higher. Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, highly metastatic and difficult to treat. For both tumor types, available treatments are generally associated to severe side effects. In our work, we explored the effect of combining metformin and propranolol, two repositioned drugs, in both tumor types. We demonstrate that treatment affects viability, epithelial-mesenchymal transition and migratory potential of CRC cells as we described before for TNBC. We show that combined treatment affects different steps leading to metastasis in TNBC. Moreover, combined treatment is also effective preventing the development of 5-FU resistant CRC. Our data suggest that combination of metformin and propranolol could be useful as a putative adjuvant treatment for both TNBC and CRC and an alternative for chemo-resistant CRC, providing a low-cost alternative therapy without associated toxicity.

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Lipoplatin Treatment in Lung and Breast Cancer

Chemotherapy Research and Practice ◽

10.1155/2011/125192 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Manuela Fantini ◽

Lorenzo Gianni ◽

Carlotta Santelmo ◽

Fabrizio Drudi ◽

Cinzia Castellani ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Triple Negative ◽

Response Rate ◽

Toxicity Profile ◽

Phase 2 ◽

Breast Cancer Patients ◽

Phase 3 ◽

Cisplatin Analogues

The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming.

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