Prexasertib in Pretreated BRCA Wild-Type High-Grade Serous Ovarian Cancer


Key Points

  • Response was observed in 33% of assessable patients.
  • Among assessable patients with platinum-resistant or -refractory disease, 32% had partial response and 26% had stable disease. 

In a phase II study reported in The Lancet Oncology by Lee et al, the investigational cell-cycle checkpoint kinase 1 and 2 inhibitor prexasertib produced responses in women with recurrent BRCA wild-type high-grade serous ovarian cancer.

In the study, 28 women with measureable disease enrolled between January 2015 and November 2016 were treated with intravenous prexasertib at 105 mg/m² given over 1 hour every 14 days in 28-day cycles. Patients had a median age of 64 years and had received a median of 5 systemic therapies; 79% had platinum-resistant or -refractory disease.

Response Rates and Adverse Events

All patients received at least one dose of prexasertib; four (14%) were not assessable for Response Evaluation Criteria in Solid Tumors (RECIST) response. A partial response was observed in 8 (33%) of 24 assessable patients (29% of the total population). Response was observed in 6 (32%) of 19 assessable patients with platinum-resistant or -refractory disease, with an additional 5 (26%) of these patients having stable disease for ≥ 6 months. Median progression-free survival in the 24 assessable patients was 7.4 months.

The most common grade 3 or 4 adverse events were neutropenia (93%), leukopenia (82%), thrombocytopenia (25%), and anemia in (11%). Grade 4 neutropenia occurred in 79% patients after the first dose of prexasertib; neutropenia in these cases was transient (median duration = 6 days and resolved without growth-factor support). Treatment-related febrile neutropenia occurred in 7% of patients.

The investigators concluded, “Prexasertib showed clinical activity and was tolerable in patients with BRCA wild-type high-grade serous ovarian carcinoma. This drug warrants further development in this setting, especially for patients with platinum-resistant or platinum-refractory disease.”

The study was funded by the Intramural Research Program of the National Institutes of Health and National Cancer Institute.

Jung-Min Lee, MD, of the Women’s Malignancies Branch, National Cancer Institute, is the corresponding author for The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.