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Trodelvy, based on Sacituzumab govitecan, for pre-treated HR+/HER2- metastatic breast cancer. Approved by European Commission


The European Commission ( EC ) has approved Trodelvy ( Sacituzumab govitecan ) as a monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine-based therapy, and at least two additional systemic therapies in the advanced setting.

The approval is based on the phase 3 TROPiCS-02 study, in which Trodelvy has demonstrated a statistically significant and clinically meaningful overall survival ( OS ) benefit of 3.2 months versus comparator single-agent chemotherapy ( treatment of physician’s choice; TPC ) ( median OS: 14.4 months vs. 11.2 months; hazard ratio [ HR ]=0.79; 95% CI: 0.65-0.96; p=0.02 ).
Trodelvy has also demonstrated a 34% reduction in risk of disease progression or death ( median PFS: 5.5 versus 4.0 months; HR: 0.66; 95% CI: 0.53-0.83; p=0.0003 ).
Three times as many people treated with Trodelvy were progression-free at one year versus those treated with chemotherapy ( 21% versus 7% ).

In the TROPiCS-02 study, Trodelvy has also significantly improved additional secondary endpoint measures, including objective response rate ( ORR ) and time to deterioration ( TTD ) assessed by the Global Health Status/Quality of Life and Fatigue scale per EORTC-QLQ-C30.
No statistically significant difference in time to deterioration in Pain Scale was observed.

The safety profile for Trodelvy is well-characterized and consistent with prior studies, with no new safety signals identified in this patient population.
In TROPiCS-02, the most frequent serious adverse reactions ( more than 1% ) were diarrhea ( 5% ), febrile neutropenia ( 4% ), neutropenia ( 3% ), and abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting ( each 2% ).
No patients treated with Trodelvy in TROPiCS-02 has experienced interstitial lung disease ( ILD ). In the TROPiCS-02 study, the discontinuation rate due to adverse reactions was 6% for Trodelvy and 4% for patients on single-agent chemotherapy.

The ESMO Living Guidelines have been updated to include Trodelvy as a category I, A, magnitude of clinical benefit ( MCBS ) score 3, for women with HR+/HER2- metastatic breast cancer.

Trodelvy is also recommended as a Category 1, preferred treatment for metastatic HR+/HER2- breast cancer by the National Comprehensive Cancer Network ( NCCN ) as defined in the Clinical Practice Guidelines in Oncology ( NCCN Guidelines ).

Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea.

Hormone receptor-positive / human epidermal growth factor receptor 2-negative ( HR+/HER2- ) breast cancer is the most common type of breast cancer and accounts for approximately 70% of all new cases.
Almost one in three cases of early-stage breast cancer eventually become metastatic, and among patients with HR+/HER2- metastatic disease, the five-year relative survival rate is 34%.
As patients with HR+/HER2- metastatic breast cancer become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy. In this setting, it is common to receive multiple lines of chemotherapy regimens over the course of treatment, and the prognosis remains poor.

TROPiCS-02 is a global, multicenter, open-label, phase 3 study, randomized 1:1 to evaluate Sacituzumab govitecan versus physicians’ choice of chemotherapy ( Eribulin, Capecitabine, Gemcitabine, or Vinorelbine ) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitor and two to four lines of chemotherapy for metastatic disease.
The primary endpoint was progression-free survival per RECIST 1.1 as assessed by blinded independent central review ( BICR ) for participants treated with Sacituzumab govitecan compared to those treated with chemotherapy. Secondary endpoints included overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures.
In the study, HER2 negativity was defined per American Society of Clinical Oncology ( ASCO ) and the College of American Pathologists ( CAP ) criteria as immunohistochemistry ( IHC ) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization ( ISH ) test.

Sacituzumab govitecan is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers.
Sacituzumab govitecan is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment. ( Xagena )

Source: Gilead, 2023

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