Novel ATR Inhibitor Under Study in Platinum-Resistant High-Grade Serous Ovarian Cancer
Posted: Wednesday, July 29, 2020
ATR kinase is activated during the DNA damage checkpoint, making it a promising target for cancers with high replication stress. Thus, researchers at the Dana-Farber Cancer Institute, Boston, tested the efficacy of the ATR kinase inhibitor berzosertib in combination with gemcitabine versus gemcitabine alone in patients with platinum-resistant high-grade serous ovarian cancer. The early results of this phase II trial, which were published in The Lancet Oncology, showed the novel agent offered a benefit in some patients, with a phase III trial in platinum-resistant ovarian cancer warranted.
First author Panagiotis A. Konstantinopoulos, MD, PhD, commented on the role of ATR in helping to repair DNA replication in a Dana-Farber press release: “Drugs that inhibit ATR—that deprive tumor cells of such repair—have the potential to be particularly effective in some cancers.”
The study comprised 70 patients with platinum-resistant high-grade serous ovarian cancer from 11 hospitals nationwide. Patients were randomly assigned to one of two treatment groups: gemcitabine or gemcitabine plus berzosertib.
The median progression-free survival with the drug combination group was 22.9 weeks, compared with 14.7 weeks with gemcitabine alone (hazard ratio = 0.57, P = .044). Adverse reactions included decreased neutrophils or platelet counts. In the gemcitabine-alone group, 14 patients (39%) had decreased neutrophils and 2 (6%) had decreased platelets, whereas in the dual-drug group, 16 (47%) had decreased neutrophils and 8 (24%) had decreased platelets.
“Our results in this phase II trial suggest that ATR inhibition in combination with chemotherapy has the potential to offer significant benefit to patients with chemotherapy-resistant high-grade serous ovarian cancer and, potentially, other tumor types where ATR plays a key role,” stated Dr. Konstantinopoulos.
Disclosure: For full disclosures of the study authors, visit thelancet.com.