Abstract
Trop-2 is an ideal candidate for targeted therapeutics because it is a transmembrane protein with an extracellular domain overexpressed in a wide variety of tumors, and is upregulated in normal cells. Consequently, several Trop-2-targeted drugs have recently been developed for clinical use, such as anti-Trop-2 antibodies. Sacituzumab govitecan, a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate, was recently approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of metastatic triple-negative breast cancer and metastatic urothelial cancer. In Italy, this treatment cannot be used in clinical practice because it has not yet been approved by the Agenzia Italiana del Farmaco (AIFA, Rome, Italy). In Italy, this is not a new problem, in fact, when a new compound is approved by the U.S. and Europe, there is often a delay in its approval for use. The adoption of universal guidelines and the standardization of Trop-2 evaluation is urgently needed.
Highlights
Sacituzumab govitecan is an antibody drug conjugate (ADC) composed by a humanized RS7 antibody targeting Trop-2 linked with SN38, a topoisomerase I inhibitor, the active metabolite of irinotecan with 100–1000-fold higher potency with respect to the parent drug [7,8]
At the 2020 San Antonio Breast Cancer Conference, in a presented biomarker analysis, it was shown that the benefit in favor of sacituzumab govitecan was maintained independently of the degree of Trop-2 expression, even if the smallest progression free survival (PFS) and overall survival (OS) difference was observed in patients with low levels of Trop-2 expression in the tumor
Superiority of sacituzumab govitecan was maintained independently from germline BRCA1/2 mutation status. These findings suggest that sacituzumab govitecan is an important option in the treatment of triple-negative breast cancer (TNBC)
Summary
The World Health Organization (WHO) estimates for Italy an incidence of 55.133 new breast cancer (BC) cases in 2020, 15–20% of them are triple-negative breast cancer (TNBC), while in the U.S, 276.480 are new BC case estimates [1,2]. Patients with metastatic triplenegative breast cancer (mTNBC) (defined by a lack of tumor-cell expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2]). Despite immunotherapy having demonstrated promising first-line clinical activity, single-agent chemotherapy represents the standard for previously treated (beyond first-line) mTNBC, even if it is associated with low response rates and short progression-free survival [5,6]. Trop-2 is a transmembrane calcium signal transducer that is highly expressed in multiple tumor types, including TNBC. Trop-2 positive mTNBC patients is fascinating and opens up new possibilities of treatment in this prognostic unfavorable population.
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