In a phase II clinical trial, patients with high-grade serous ovarian cancer who were treated with berzosertib and chemotherapy lived substantially longer than did those treated with chemotherapy alone.
Researchers at Dana-Farber Cancer Institute are conducting the study. The findings were published in The Lancet Oncology.
“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 HGSOC and, potentially, other tumor types where ATR plays a key role,” lead author Panagiotis Konstantinopoulos, director of translational research, Gynecologic Oncology, at Dana-Farber, said in a statement.
In the study, investigators at 11 cancer centers around the country enrolled 70 patients with HGSOC that was resistant to platinum-based chemotherapy. Half the participants were randomly assigned to receive the standard chemotherapy agent gemcitabine alone and half received gemcitabine in combination with berzosertib.
“The unbridled growth of cancer cells places enormous stress on the process of DNA replication,” Konstantinopoulos said. “ATR helps them survive that stress: its job is to coordinate the halting of the cell cycle to check if the DNA is intact or needs repair. Drugs that inhibit ATR – that deprive tumor cells of such repair – have the potential to be particularly effective in some cancers.”
The estimated median progression-free survival of patients receiving gemcitabine alone – the period in which their disease was in retreat or stable—was 14.7 weeks. For those receiving gemcitabine and berzosertib, it was 22.9 weeks. Among patients with the most platinum resistant tumors (i.e. those who had progressed within 3 months from prior platinum-based chemotherapy), the difference was even greater: 9 weeks for gemcitabine versus 27.7 weeks for gemcitabine and berzosertib.
