CHK1 Inhibitor in BRCA Wild-Type Triple-Negative Breast Cancer
Posted: Wednesday, September 9, 2020
According to research published in The Oncologist, monotherapy with prexasertib, a second-generation cell-cycle checkpoint kinase 1 (CHK1) inhibitor, resulted in modest clinical activity in patients with triple-negative breast cancer. Jung-Min Lee, MD, of the National Institutes of Health, and colleagues noted that the study highlights “the unmet need for combination treatment strategies.”
The phase II trial included nine patients with germline BRCA wild-type, metastatic or recurrent triple-negative breast cancer who had undergone at least one prior treatment. Each patient received 105 mg/m2 of intravenous prexasertib every 2 weeks.
The overall response rate was 11.1%, with one patient achieving a partial response, and four patients experiencing stable disease; the median progression-free survival was 86 days. According to pharmacodynamic analysis, prexasertib resulted in damage to the DNA of peripheral immune cells and caused a reduction in activated or reinvigorated CD8 T cells. Despite a T-cell decrease, the sole patient achieving a partial response did show evidence of having experienced T-cell recovery.
The most common grade 3 or 4 treatment-related adverse events included afebrile neutropenia, anemia, and thrombocytopenia. Adverse events were found to be manageable with the use of supportive care measures. The use of prophylactic granulocyte colony-stimulating factor was also recommended for consideration to avoid treatment delays or the need for dose reductions.
Disclosure: The study authors reported no conflicts of interest.