Literature Express No. 18,
Original Xi'an Daxing Nail Milk Li Gang Nail Milk Love 2022-02-06 12:23
Triple-negative breast cancer also has targeted drugs? Yes, you heard that right.
The ASCENT study demonstrated for the first time that Trop-2 ADC gosartozumab can significantly improve PFS and OS in patients treated with multi-line treatment of drug-resistant mTNBC, opening up the possibility of new ADC drugs for mTNBC.
Subsequently, ADC drugs with different targets are exploring the efficacy and safety of mTNBC, including SGNLVA-001, Dato-DXd and HER3-DXd, etc., and the ongoing Phase III clinical research is worth looking forward to.
Let's look at the literature!
background
Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan (goshatozumab) is an antibody-drug conjugate consisting of an antibody against the human vegetative cell surface antigen 2 (Trop-2) expressed in most breast cancers, coupled to sn38 (topoisomerase I inhibitor) by a patented hydrolyzed linker.
method
In this randomized Phase 3 trial, we evaluated the efficacy of sacituzumab govitcan with doctor-selected single-agent chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with recurrent or refractory metastatic triple-negative breast cancer. The primary endpoint was progression-free survival in patients with no brain metastases (as determined by a blind independent center review).
outcome
A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitcan (235 patients) or chemotherapy (233 patients). The average age was 54 years; All patients have been on taxane drugs. Median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) and 1.7 months (95% CI, 1.5 - 2.6; 150 events) (risk ratio for disease progression or death, 0.41; 95% CI, 0.32 ~ 0.52; Intraoperative, 0.001). The median overall survival of sacituzumab govitcan was 12.1 months (95% CI, 10.7 to 14.0) and the median overall survival of chemotherapy was 6.7 months (95% CI, 5.8 to 7.7) (risk-to-risk ratio of death, 0.48; 95% CI: 0.38 ~ 0.59; Intraoperative, 0.001). The objective response rate was 35% in patients with sacituzumab govitcan and 5% in chemotherapy patients. The incidence of major treatment-related adverse events of grade 3 or above was neutropenia (51% for sacituzumab govitcan and 33% for chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were 3 deaths due to adverse events in each group; No deaths are thought to be associated with sacituzumab govitcan treatment.
conclusion
In patients with metastatic triple-negative breast cancer, the progression-free and overall survival of the sacituzumab govitcan treatment group was significantly longer than that of the single-agent chemotherapy group. The combination of sacituzumab and govitcan is more prone to bone marrow suppression and diarrhea.
Icon. Efficacy outcomes in patients without brain metastases at baseline and in the population at large.
Figures A and B show progression-free survival and overall survival in patients without brain metastases, respectively. Progression-free survival was determined by blinding independent center evaluation according to the criteria for evaluating efficacy of solid tumors (version 1.1). Group C showed a waterfall chart of the optimal percentage change in the total diameter of target lesions in patients with no brain metastases who had been assessed by the central review at least one response (212 patients in the sacituzumab govitcan group and 160 patients in the chemotherapy group). An asterisk at 0 indicates that there is no change in patient tumor size compared to baseline. Figure D shows progression-free survival for all randomly assigned patients (with or without brain metastases).
Gosartozumab
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