Sacituzumab govitecan and radiotherapy in metastatic, triple-negative, and BRCA-mutant breast cancer patient with active brain metastases: A case report

Abstract

BackgroundTriple-negative breast cancer (TNBC) is an aggressive cancer subtype, owing to its high metastatic potential: Patients who develop brain metastases (BMs) have a poor prognosis due to the lack of effective systemic treatments. Surgery and radiation therapy are valid options, while pharmacotherapy still relies on systemic chemotherapy, which has limited efficacy. Among the new treatment strategies available, the antibody-drug conjugate (ADC) sacituzumab govitecan has shown an encouraging activity in metastatic TNBC, even in the presence of BMs.Case presentationA 59-year-old woman was diagnosed with early TNBC and underwent surgery and subsequent adjuvant chemotherapy. A germline pathogenic variant in BReast CAncer gene 2 (BRCA2) was revealed after genetic testing. After 11 months from the completion of adjuvant treatment, she had pulmonary and hilar nodal relapse and began first-line chemotherapy with carboplatin and paclitaxel. However, after only 3 months from starting the treatment, she experienced relevant disease progression, due to the appearance of numerous and symptomatic BMs. Sacituzumab govitecan (10 mg/kg) was started as second-line treatment as part of the Expanded Access Program (EAP). She reported symptomatic relief after the first cycle and received whole-brain radiotherapy (WBRT) concomitantly to sacituzumab govitecan treatment. The subsequent CT scan showed an extracranial partial response and a near-to-complete intracranial response; no grade 3 adverse events were reported, even if sacituzumab govitecan was reduced to 7.5 mg/kg due to persistent G2 asthenia. After 10 months from starting sacituzumab govitecan, a systemic disease progression was documented, while intracranial response was maintained.ConclusionsThis case report supports the potential efficacy and safety of sacituzumab govitecan in the treatment of early recurrent and BRCA-mutant TNBC. Despite the presence of active BMs, our patient had a progression-free survival (PFS) of 10 months in the second-line setting and sacituzumab govitecan was safe when administered together with radiation therapy. Further real-world data are warranted to confirm sacituzumab govitecan efficacy in this patient population.

The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy—A Retrospective Multi-Center Cohort Study

“…The literature review of published data resulted in five publications, including one abstract on real-world experience with SG [15], three clinical case reports [16][17][18], and one single-center case series [19] [Figure 1].…”

“…No grade 3 adverse events were reported, but SG was reduced to 7.5 mg/kg due to persistent grade 2 asthenia. After 10 months from starting SG, systemic disease progression was documented, while intracranial response was maintained [16]. Di Mauro et al report on the case of a 59-year-old woman with a BRCA mutation and metastatic TNBC, who was treated with SG and radiotherapy [16].…”

“…After 10 months from starting SG, systemic disease progression was documented, while intracranial response was maintained [16]. Di Mauro et al report on the case of a 59-year-old woman with a BRCA mutation and metastatic TNBC, who was treated with SG and radiotherapy [16]. The patient received SG (10 mg/kg on days 1 and 8 every 21 days) as palliative second-line treatment as part of an Expanded Access Program.…”

“…No grade 3 adverse events were reported, but SG was reduced to 7.5 mg/kg due to persistent grade 2 asthenia. After 10 months from starting SG, systemic disease progression was documented, while intracranial response was maintained [16].…”

Breast Cancer with Brain Metastasis: Molecular Insights and Clinical Management

“…At the moment, the treatment strategy for most TNBCs relies on chemotherapy, immunotherapy (if PD-L1 is positive), and target therapy with poly (adenosine diphosphate–ribose) polymerase inhibitors (PARPis) based on germline BRCA1/2 ( gBRCA1/2 ) status. [ 85 , 106 , 107 , 108 ]. In patients with MBC harboring a gBRCA1/2 pathogenetic variant, the two PARPis, talazoparib and olaparib, showed a benefit in survival outcomes [ 109 ].…”