Triple-negative breast cancer: an effective therapeutic innovation is a game changer
Published in The New England Journal of Medicine, these very positive results give a glimpse of a revolution in treatment of patients in the coming years.
Triple-negative breast cancer affects between 10 and 15% of breast cancer patients, and is more aggressive with higher risk of metastasis. Among these patients, a small sub-group (patients with a BRCA1 or BRCA2 mutation, or around 15% of them) have access to a targeted therapy (PARP inhibitors), but the others are still awaiting effective therapeutic solutions.
Among the options explored, Institut Curie has been assessing antibody-drug conjugates for several years now; these are molecules that combine an antibody with chemotherapy, which helps direct the chemotherapy to the core of the tumor cells.
The international phase-3 ASCENT clinical trial began in 2017, and included 468 patients suffering from advanced triple-negative breast cancer who had already received several lines of treatment. This clinical trial evaluated Sacituzumab govitecan,an antibody-drug conjugate, in comparison with traditional chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine). The results of the study revealed median survival without progression of 5.6 months with the antibody-drug conjugate (compared with 1.7 months with chemotherapy). As for overall survival, it reached 12.1 months with Sacituzumab govitecan compared with 6.7 months with traditional chemotherapy. Furthermore, the percentage of patients with an objective response was 35% with the antibody-drug conjugate, versus 5% with chemotherapy.
With overall survival doubled, I believe this is the positive and encouraging result we have seen in many years for patients with triple-negative breast cancer. I am now convinced that this new class of drug will change the outlook in the coming years. However, we will have to face another hurdle, since we have to wait several months for approval for Sacituzumab govitecan to be granted in France, so that we can prescribe this new therapy to our patients.
announced Delphine Loirat, medical oncologist at Institut Curie and principal investigator in the ASCENT studyDelphine Loirat,
Many clinical trials with antibody-drug conjugates are ongoing, including at Institut Curie, where we currently have 7 trials ongoing or in follow-up. Thus Sacituzumab govitecan is under trial for the earliest stages of the disease, though other molecules are also being evaluated for triple-negative breast cancer (for example Trastuzumab deruxtecan) or for other types of cancer (hormone-dependent breast cancer, bladder cancer, lung cancer, etc.).
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. A. Bardia, S.A. Hurvitz, S.M. Tolaney, D. Loirat, K. Punie, M. Oliveira, A. Brufsky, S.D. Sardesai, K. Kalinsky, A.B. Zelnak, R. Weaver, T. Traina, F. Dalenc, P. Aftimos, F. Lynce, S. Diab, J. Cortés, J. O’Shaughnessy, V. Diéras, C. Ferrario, P. Schmid, L.A. Carey, L. Gianni, M.J. Piccart, S. Loibl, D.M. Goldenberg, Q. Hong, M.S. Olivo, L.M. Itri, and H.S. Rugo, for the ASCENT Clinical Trial Investigators. New England Journal of Medicine 2021; 384:1529-1541 / DOI: 10.1056/NEJMoa2028485
The ASCENT trial is funded by Immunomedics: ClinicalTrials.gov number: NCT02574455
 Sacituzumab govitecan is composed of an antibody that targets Trop2: a cell surface antigen (expressed in several solid cancers, and more particularly in triple-negative breast cancer), coupled to a topoisomerase inhibitor.