22 Apr Triple Negative Breast Cancer: TRODELVY® (sacituzumab govitecan) Trial Demonstrates Significant Improvement Compared to Standard Chemo
MedicalResearch.com Interview with:
Aditya Bardia MD, MPH
Director, Breast Cancer Research Program,
Attending Physician, Massachusetts General Hospital
Harvard Medical School
MedicalResearch.com: What is the background for this study?
Response: Triple negative breast cancer (TNBC) represents an aggressive subtype of breast cancer associated with guarded prognosis. For patients with pre-treated metastatic TNBC, standard chemotherapy is associated with low response rate (5-10%) and poor progression-free survival (2-3 months), highlighting need for better therapies.
Sacituzumab govitecan is an antibody drug conjugate (ADC) which combines SN-38, an active metabolite of irinotecan, with an antibody against Trop-2, an antigen overexpressed in majority of triple negative breast cancer.
MedicalResearch.com: What are the main findings?
Response: The ASCENT trial was a global phase 3 randomized clinical trial that randomly assigned 529 patients to sacituzumab govitecan or treatment of their physician’s choice (eribulin, vinorelbine, gemcitabine, or capecitabine). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival, objective response rate, and safety. The ASCENT study met its primary endpoint of improvement in PFS. The median PFS was 5.6 months in the sacituzumab govitecan-hziy arm vs 1.7 months in the standard chemotherapy arm. A benefit with sacituzumab govitecan was seen in all subgroups, including those based on age (<65 years vs ³65 years), race, number of prior lines of therapy, geographic region, prior use of PD-L1 or PD-1, and presence of liver metastases.
Overall survival was also improved among patients treated with sacituzumab govitecan. The median overall survival was 12.1 months with sacituzumab govitecan vs 6.7 months with standard chemotherapy. This difference corresponded to a hazard ratio of 0.48, which was highly statistically significant (P<.0001). The objective response rate was 35% with sacituzumab govitecan vs 5% with standard chemotherapy (P<.0001). The key grade 3 treatment-related adverse events associated with sacituzumab govitecan included neutropenia, diarrhea, anemia, and febrile neutropenia. There were no treatment-related deaths in the sacituzumab govitecan arm. The rate of adverse events leading to treatment discontinuation was low for both arms, at 4.7% with sacituzumab govitecan and 5.4% with treatment of the physician’s choice.
MedicalResearch.com: What should readers take away from your report?
Response: ASCENT is the first clinical trial with an antibody-drug conjugate to demonstrate a significant improvement compared with standard chemotherapy in pretreated metastatic triple-negative breast cancer. Previously, the FDA had granted accelerated approval to sacituzumab govitecan for patients with metastatic triple negative breast cancer based on objective response rate and duration of response results in a Phase 1/2 study. Based on results of the phase 3 ASCENT trial, the FDA granted full approval to sacituzumab govitecan on April 7th 2021.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: There is need to investigate the efficacy of sacituzumab govitecan in earlier lines, including patients with localized TNBC.
COIs: Consulting/advisory board: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Taiho, Sanofi, Diiachi Pharma/Astra Zeneca, Puma , : Biothernostics Inc., Phillips, Eli Lilly, Foundation Medicine.
Contracted Research/Grant (to institution): Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Diiachi Pharma/Astra Zeneca.
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer
Aditya Bardia, M.D., Sara A. Hurvitz, M.D., Sara M. Tolaney, M.D., M.P.H., Delphine Loirat, M.D., Ph.D., Kevin Punie, M.D., Mafalda Oliveira, M.D., Ph.D., Adam Brufsky, M.D., Ph.D., Sagar D. Sardesai, M.D., Kevin Kalinsky, M.D., Amelia B. Zelnak, M.D., Robert Weaver, M.D., Tiffany Traina, M.D., for the ASCENT Clinical Trial Investigators
April 22, 2021
N Engl J Med 2021; 384:1529-1541
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