TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer.
Journal
Future oncology (London, England)
Journal Volume
20
Journal Issue
8
Start Page
423
End Page
436
ISSN
1744-8301
Date Issued
2024-03
Author(s)
Bardia, Aditya
Jhaveri, Komal
Kalinsky, Kevin
Pernas, Sonia
Tsurutani, Junji
Xu, Binghe
Hamilton, Erika
Im, Seock-Ah
Nowecki, Zbigniew
Sohn, Joohyuk
Laurentiis, Michelino De
Jañez, Noelia Martínez
Adamo, Barbara
Lee, Keun Seok
Jung, Kyung Hae
Rubovszky, Gábor
Tseng, Ling-Ming
Yuan, Yuan
Maxwell, Micah J
Haddad, Vincent
Khan, Sabrina S
Rugo, Hope S
Pistilli, Barbara
Abstract
Improving the prognosis for patients with metastatic HR+/HER2- breast cancer remains an unmet need. Patients with tumors that have progressed on endocrine therapy and/or are not eligible for endocrine therapy had limited treatment options beyond chemotherapy. Antibody-drug conjugates are a novel and promising treatment class in this setting. Datopotamab deruxtecan (Dato-DXd) consists of a TROP2-directed humanized IgG1 monoclonal antibody attached a serum-stable cleavable linker to a topoisomerase I inhibitor payload. TROPION-Breast01 is an ongoing phase III study that is evaluating the efficacy and safety of Dato-DXd compared with investigator's choice of standard-of-care chemotherapy in patients with inoperable or metastatic HR+/HER2- breast cancer who have received one or two prior lines of systemic chemotherapy in the inoperable or metastatic setting. NCT05104866 (ClinicalTrials.gov).
Antibody-drug conjugates are a type of drug with two parts: an antibody that directs the drug to the cancer cells and a cancer-cell killing toxic payload. By binding to cancer cells before releasing the payload, treatment is directed to the site of action so there are fewer side effects in the rest of the body. Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugates made up of datopotamab (antibody) and DXd (payload) which are joined together a stable linker. Datopotamab binds to a protein found on cancer cells called TROP2; it then goes inside and releases the DXd payload to kill the tumor cells. DXd may leak out to surrounding cancer cells and kill those as well. The TROPION-Breast01 study is comparing Dato-DXd with standard-of-care chemotherapy. Around 700 patients will take part, who have: Tumors that cannot be surgically removed. Tumors that are hormone receptor-positive and do not have HER2 overexpression. Had one or two lines of previous chemotherapy (after the tumor could not be surgically removed, or had spread). Had tumor growth despite hormonal therapy or are ineligible for hormonal therapy. Patients who meet the entry criteria will be randomly assigned to a treatment group in equal numbers to either Dato-DXd or an appropriate chemotherapy, out of four options chosen by the treating doctor. At the end of the study, researchers will look at whether the patients who receive Dato-DXd live longer without their breast cancer getting worse, compared with patients who receive chemotherapy. This study is also looking at how the treatment affects patients' quality of life.
Subjects
ADC
Dato-DXd
HR-positive/HER2-negative
TROP2
Trophoblast cell surface antigen 2
antibody-drug conjugate
datopotamab deruxtecan
inoperable breast cancer
metastatic breast cancer
SDGs
Type
journal article