Recent Adavosertib Results in Ovarian Cancer Could Be Sign of Things to Come

New results involving the Wee1 inhibitor adavosertib brought improved survival benefits in a hard-to-treat type of ovarian cancer, but trials in the pipeline suggest the positive findings could be just the beginning.

Investigators reported last week that adavosertib to the chemotherapy gemcitabine reduced the risk of disease progression and death in women with relapsed, platinum-resistant or refractory ovarian cancer. The phase 2 results appeared in The Lancet.

The study involved 124 women, of whom 99 had high-grade serious ovarian cancer. They were randomized 2:1 to receive adavosertib plus gemcitabine (65 patients) or placebo plus gemcitabine (34 patients). Another 25 women were placed in an exploratory cohort. After randomization, 5 women (4 taking the study drug, 1 in the placebo group), were found ineligible and did not receive treatment. Median age for treated patients was 62 years.

Progression-free survival was 4.6 months in the group taking adavosertib, compared with 3.0 months for the group taking gemcitabine only, for a hazard ratio of 0.55 (95% CI, 0.35-.90, P = .015). An accompanying editorial noted the dose-response relationship and relatively manageable toxicity.

“This study realizes the potential of targeting the cell cycle derangement present in a substantial subpopulation of patients with resistant ovarian cancer," the editorial stated. “The development of rapid immunohistochemical or circulating biomarkers to identify this subpopulation could herald the more widespread use of cell cycle targeting therapies like adavosertib earlier in the disease course.”

The trial ran from September 2014 to May 2018, with a start date just before the PARP inhibitor olaparib was approved for the treatment of ovarian cancer for patients with germline BRCA ovarian cancer who had received at least 3 prior lines of therapy. PARP inhibitors, and olaparib in particular, have proven to be game-changers in BRCA-driven ovarian cancer.

According to the National Cancer Institute, there are now several trials under way involving adavosertib with olaparib. Since 2014, olaparib has received FDA approval in other indications for ovarian cancer, including a May 2020 approval for maintenance treatment, either as a monotherapy or in combination with bevacizumab.

According to the NCI website, trials involving adavosertib and olaparib in ovarian cancer and other solid tumors include:

• Recurrent ovarian, primary peritoneal, or fallopian tube cancer. Currently active at MD Anderson Cancer Center at The University of Texas and Dana-Farber Cancer Institute, this phase 2 trial is examining whether adavosertib and olaparib may stop the growth of tumor cells inhibiting the action of enzymes needed for cell growth.
• STAR Study. This phase 1 trial is examining dosing and side effects of adavosertib when given after olaparib when patients have solid tumors that have spread to other parts of the body. This is also taking place at MD Anderson.
• Advanced solid tumors. This phase 2 study involves olaparib with or without adavosertib and 2 other targeted therapies in treating patients whose solid tumors have spread to other parts of the body. This trial is taking place at 4 locations, although it is temporarily not accruing new patients: Yale, Dana-Farber Cancer Institute, Cleveland Clinic, and Vanderbilt.