High-grade serous ovarian cancer is associated with increased replication stress that makes cells vulnerable to ATR inhibition and other adverse outcomes. This study aims to evaluate the efficacy and acceptable toxicity of berzosertib, a selective ATR inhibitor, along with gemcitabine in the treatment of platinum-resistant high-grade serous ovarian cancer.

This multicenter, randomized, open-label, phase 2 study included a total of 70 patients with recurrent, platinum-resistant high-grade serous ovarian cancer. The patients were randomly assigned in a 1:1 ratio to receive berzosertib-gemcitabine combination therapy (n=34) or gemcitabine alone (n=36). The primary outcome of the study was progression-free survival (investigator-assessed).

During the median follow-up of 53.2 weeks in the combination group, the median progression-free survival was 22.9 weeks, as compared with 12.7 weeks in the gemcitabine alone group during a median follow-up of  43.0 weeks. Commonly occurring treatment-related grade 3 & 4 events were decreased neutrophil count and decreased platelet count in the two groups. One treatment-related death due to sepsis occurred in the gemcitabine alone group, and one 1 treatment-related death due to pneumonitis occurred in the combination group.

The research concluded that combination therapy of berzosertib and gemcitabine could be beneficial in improving overall progression-free survival in patients with platinum-resistant high-grade serous ovarian cancer.

Ref: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30180-7/fulltext