Clinical trial results from the randomized, non-comparative Phase II EFFORT study showed that adavosertib, a Wee1 inhibitor, was effective in patients with PARP inhibitor-resistant ovarian cancer when given alone and in combination with olaparib, a PARP inhibitor.
This trial was based on early research demonstrating that resistance to PARP inhibitors may be reversed by the inhibition of Wee1, a protein kinase that has become a viable therapeutic target in cancer due to its role in regulating DNA damage repair pathways and checkpoints.
The study enrolled 80 patients with recurrent ovarian, fallopian tube or primary peritoneal cancer with documented progressive disease on a PARP inhibitor. In patients who only received adavosertib, the drug achieved an overall response rate (ORR) of 23% and a clinical benefit rate (CBR) of 63%, while patients who received the adavosertib-olaparib combination had an ORR of 29% and a CBR of 89%.
Several PARP inhibitors have been approved by the Food and Drug Administration for ovarian cancer over the past few years and their use in cancer therapy has increased over time, but cancer cells can develop a resistance to this new class of drug that reduces their therapeutic effectiveness.
“These results meet a critical unmet need. Clinically, we have observed innate resistance in patients who we would expect to benefit from a PARP inhibitor. Conversely, there are patients who may initially benefit but then ultimately have disease progression,” said Shannon Westin, M.D., associate professor of Gynecologic Oncology and Reproductive Medicine, who will present results of the study. “These two populations of patients are growing, and we’re seeing them in our clinic every day.”
Larger randomized trials will be required to better understand the efficacy of the drugs, as well as to determine which patients need a single agent or combination therapy.
ASCO 2021: Abstract #5505