Research has also shown activity with sacituzumab govitecan in subsets of patients with triple-negative breast cancer, such as those with active brain metastases.
Developing research shows a significant benefit for sacituzumab govitecan in patients with triple-negative breast cancer (TNBC), according to a presentation at the American Society of Clinical Oncology 2021 Annual Meeting.
Sacituzumab govitecan is an antibody drug conjugate (ADCs), according to presenter Foluso O. Ademuyiwa, MD, MPH, an associate professor at the Washington University School of Medicine in St. Louis. ADCs are monoclonal antibodies conjugated to cytotoxic agents via a linker and have tumor specificity and potency that is not usually achievable with other agents.
Thus far, Ademuyiwa said sacituzumab govitecan has been approved for the target antigen TROP-2 in metastatic TNBC with 2 or more prior systemic therapies, including at least one for metastatic disease. Most recently, it was approved earlier in 2021 for the treatment of urothelial cancer.
In the ASCENT phase 3 trial of patients with metastatic TNBC, investigators found a median progression-free survival of 5.6 months among patients receiving sacituzumab govitecan, compared with 1.7 months in patients receiving a standard treatment of the physician’s choice. Similar benefits were found in some important subgroups, including heavily pre-treated patients with more than 3 prior lines of therapy, patients with prior checkpoint inhibitor therapies, and patients who were not triple-negative at the time of diagnosis.
The overall survival (OS) results also favored treatment with sacituzumab govitecan, with a nearly doubled OS of 12.1 months compared to 6.7 months in the standard of care arm. Notably, a cohort of patients with active brain metastases also had better outcomes with sacituzumab govitecan with regard to clinical benefit rate. Ademuyiwa noted that there is an ongoing study in this patient population.
Reported adverse effects (AEs) of sacituzumab govitecan include neutropenia, leukopenia, anemia, lymphopenia, febrile neutropenia, diarrhea, nausea, vomiting, fatigue, alopecia, decreased appetite, and urinary tract infection. Two trials investigating the drug in metastatic TNBC saw an approximately 5% discontinuation rate due to AEs.
Ademuyiwa addressed febrile neutropenia and grade 3 or 4 diarrhea specifically, both of which have a black box warning with sacituzumab govitecan. Febrile neutropenia and neutropenia can be managed proactively with dose modifications, Ademuyiwa said, whereas grade 3 or 4 diarrhea should prompt a workup for infectious diseases and can also be managed with medications.
Finally, Ademuyiwa said there are many ongoing studies investigating the use of sacituzumab govitecan in all settings. For example, the NeoSTAR trial is investigating it in the neoadjuvant setting with localized TNBC and the SASCIA study is evaluating its use in primary human epidermal growth factor receptor 2-negative breast cancer with high relapse risk following standard neoadjuvant treatment.
Ademuyiwa FO. FDA Approvals and Their Incorporation into Clinical Practice. Presented at: American Society of Clinical Oncology 2021 Annual Meeting. June 4, 2021. Accessed June 4, 2021.