Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that accounts for approximately 15% of all breast cancers. It is more common in younger and premenopausal women. Triple-negative means that the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are all negative.
Due to the lack of therapeutic targets, as well as its high histological grade and aggressiveness, triple-negative breast cancer is known as the "most dangerous breast cancer." In particular, patients with metastatic triple-negative breast cancer have an average survival of only 18 months or even less from the date of metastatic diagnosis.
TROP-2 is highly expressed in various human epithelial cancers, including breast cancer, lung cancer, gastric cancer, colorectal cancer, pancreatic cancer, prostate cancer, cervical cancer, head and neck cancer, and ovarian cancer. TROP-2 overexpression plays a crucial role in tumor growth. Furthermore, in several cancers, including breast cancer, high TROP-2 expression has been found to be associated with more aggressive disease and poor prognosis.
Trodelvy is an ADC drug composed of an antibody targeting TROP-2 connected to SN-38, the active metabolite of the chemotherapy drug Irinotecan. It can bind to the TROP-2 protein to deliver the active metabolite of the chemotherapy drug irinotecan to the inside of cancer cells.
On May 6, 2022, the online medical journal OncLive published the latest results of the Phase III ASCENT trial (NCT02574455), which evaluated the efficacy and safety of Trodelvy, an antibody-drug conjugate (ADC) targeting TROP-2, in patients with metastatic triple-negative breast cancer (TNBC).
Previously 2021 On April 8th of the year, in the United States FDA Approved Trodelvy It is marketed for the treatment of adult patients with unresectable locally advanced or metastatic triple negative breast cancer who have previously received at least two treatments, including at least one treatment for metastatic diseases. This is FDA The first approved treatment for triple negative breast cancer ADC Drug, also the world's first approved targeted drug TROP-2 Antibody conjugated drugs.
Product name: Trodelvy
Common name: sacituzumab govitecan-hziy
Target: TROP-2
Specification: 180mg
First approval in the United States: April 2020
Approved indications: Triple negative breast cancer
Recommended dose: 10mg/kg, once a week, intravenously on the 1st and 8th days (a course of treatment every 21 days).
Storage conditions: Store in cold storage at 2-8℃
Clinical data
In this trial, a total of 529 patients participated in the trial. 61 patients had brain metastases at baseline, and 468 patients had no evidence of brain metastases. Among these patients, 267 patients received Trodelvy treatment and 262 patients received chemotherapy (irepilin, vinorubine, capecitabine, gemcitabine).
In the analysis, the researchers stratified the patients by measuring HER2 expression through an immunohistochemistry (IHC) score. Low expression of HER2 is defined as a person with an IHC score of 1+ or 2+; negative HER2 is defined as an IHC score of 0.
The main endpoint of the study was progress-free survival (PFS); secondary endpoints included: total survival (OS), total objective remission rate (ORR), duration of remission (DOR), and quality of life.
The test results showed that in patients with triple-negative breast cancer with low expression of HER2, Trodelvy significantly improved PFS compared with the chemotherapy group. The specific data are as follows, the median PFS is 6.2 months VS. 2.9 months; for HER2-negative patients, the median PFS of the Trodelvy group vs. the chemotherapy group is 4.3 months VS. 1.6 months.
In addition, compared with the chemotherapy group, Trodelvy significantly increased the OS of patients and reduced the risk of death of patients with low HER2 expression by 57%. Specifically, in this patient group, the median OS of the Trodelvy group vs. the chemotherapy group was 14.0 months VS. 8.7 months. In HER2-negative patients, the median OS is 11.3 months VS. 5.9 months.
In the targeted therapy (ITT) population, the median PFS of the Trodelvy group vs. the chemotherapy group was 4.8 months VS. 1.7 months; the median OS was 11.8 months VS. 6.9 months.
ORR is comparable in different populations. In the ITT population, the ORR was 31% VS. 4%; the ORR of patients with low HER2 expression was 32% VS. 8%; and the ORR of patients with HER2 negative was 31% VS. 3%.
Among patients with low HER2 expression, the complete remission (CR) rate of the Trodelvy group vs. the chemotherapy group was 5% VS. 2%, the partial remission (PR) rate was 27% VS. 7%, and the disease stability (SD) rate was 37% VS. 40%. ; The median DOR is 5.6 months VS. 3.6 months; the clinical benefit rate (CBR) is 68% VS. 45%.
Among HER2-negative patients, the CR rate of the Trodelvy group vs. the chemotherapy group was 2% VS. 0%, the PR rate was 29% VS. 3%, and the SD rate was 37% VS. 23%; the median DOR was 6.9 months VS. 2.9 months; CBR was 68% VS. 26%.
In the ITT population, the CR rate of the Trodelvy group vs. the chemotherapy group was 4% VS. 1%, the PR rate was 27% VS. 3%, and the SD rate was 36% VS. 27%; the median DOR was 6.3 months VS. 3.6 months; CBR was 67% VS. 31%.
Summary
According to the latest analysis results of the ASCENT trial, regardless of HER2 expression, Trodelvy maintained clinical benefits in patients with metastatic triple-negative breast cancer.
Reference source：
https://www.onclive.com
