N Engl J Med 2021 Apr 22
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.
Abstract
Background
Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker.
Methods
In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases.
Results
A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment.
Conclusions
Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).
Related Questions
In previously untreated patients with mTNBC, what is your protocol for prophylactic GCSF use for sacituzumab govitecan?
Sacituzumab govitecan (SG) causes grade 3 or higher neutropenia in 47% of patients and neutropenic fever in 7%. It has a boxed warning for neutropenia and recommends primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) for all patients at increased risk of febrile neutropenia. Fata...
How do you select first-line therapy for PD-L1-positive metastatic TNBC?
At this point, we only have mature data on pembro and SG, and this is the regimen I would use.
What factors do you use to decide between trastuzumab-deruxtecan and sacituzumab govitecan in HER2-low metastatic breast cancer?
Updated answer - 11/26/2024There is currently limited data to guide the efficacy of trastuzumab deruxtecan (T-DXd) after progression on sacituzumab or vice versa. Since both drugs have a topoisomerase 1 inhibitor payload, cancers resistant to topoisomerase 1 inhibitors may be resistant to both drugs...
What criteria would you use to decide between trastuzumab-deruxtecan and sacituzumab govitecan in HER2 low metastatic TNBC given T-DXd approval in HER2 low breast cancer?
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If there is HER2-low discordance between primary and subsequent breast cancer biopsies, in which scenarios would you choose to use trastuzumab deruxtecan?
Because of the potential heterogeneity of HER2 expression, I would still offer T-DXd for these patients. In addition, HER2 IHC 0 may not exclude T-DXd activity based on the DAISY trial.
How will you approach treatment sequencing and use of trastuzumab deruxtecan in hormone receptor-negative, HER2-low breast cancer?
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How has the ASCENT trial impacted your management of previously treated metastatic TNBC?
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How do you counsel patients with metastatic TNBC on their various treatment options after progression on first line regimens?
The choice of a regimen would typically weigh: Expected efficacy. It is important to acknowledge that outside of the 1st and 3rd line settings, there may not be much data to guide the selection of one regimen over another. Expected toxicity. This includes side effects such as neuropathy, etc but wo...
In which scenarios would you utilize sacituzumab govitecan earlier than third line in the treatment of metastatic TNBC?
To date, we do not have a head-to-head comparison of sacituzumab govitecan prior to the 3rd line setting and insurance approval for sacituzumab govitecan prior to 3rd can be a barrier. However, I consider it under the following circumstances: The patient has significant pre-existing neuropathy. Many...
Are there known biomarkers predictive of response or resistance to sacituzumab govitecan which should be incorporated into treatment decisions for metastatic TNBC?
In the ASCENT trial, we evaluate the association between Trop-2 expression and clinical outcomes. Overall, the median progression-free survival (PFS) was 6.9, 5.6, and 2.7 months for high, medium, and low Trop-2 scores, respectively with SG compared with 2.5, 2.2, and 1.6 months with standard chemot...
How do you address and mitigate neutropenia in patients with TNBC receiving sacituzumab govitecan in 3rd line or beyond?
For those who develop neutropenia, I generally use neulasta after day 8, but I don't use it with cycle 1 in all comers, unless they are heavily pre-treated and already have a relatively low ANC prior to starting treatment.
How do you treat leptomeningeal disease in metastatic HR+ HER2- breast cancer?
Survival after a diagnosis of leptomeningeal metastasis (LM) remains poor. Radiation therapy remains a primary therapy for breast cancer LM. Intrathecal therapy has resulted in limited efficacy and is associated with significant toxicity. Limited data regarding the efficacy of systemic therapies in ...
Would you consider treatment with sacituzumab in triple negative metastatic breast cancer if there has been progression on irinotecan?
While I am not aware of any data on the efficacy of sacituzumab govitecan (SG) in such patients, not surprising since irinotecan is not commonly administered to such patients, I would not rule out a trial of this agent. We know that ado-trastuzumab emtansine can be effective in patients progressing ...