In a phase II trial reported in the Journal of Clinical Oncology, Fu et al found that the WEE1 kinase inhibitor adavosertib was active in patients with refractory solid tumors with CCNE1 amplification, with evidence of increased activity in epithelial ovarian cancer.
Study Details
In the trial, 30 eligible patients were enrolled at six National Cancer Institute Experimental Therapeutics Clinical Trials Network cancer centers between January 2019 and May 2020. Patients received adavosertib at 300 mg once daily on days 1 to 5 and 8 to 12 of 21-day cycles.
Tumor types included epithelial ovarian cancer in 14 patients, breast cancer in 3, uterine cancer in 3, and 10 different types in 1 patient each. The median number of prior systemic therapies was three (range = 1–7). The primary endpoint was objective response rate.
Responses
Median follow-up was 9.9 months. Objective responses (all partial) were observed in eight patients (27%, 95% confidence interval [CI] = 12%–46%). An additional three patients had stable disease for ≥ 6 months, yielding an objective response/stable disease ≥ 6 months rate of 37% (95% CI = 20%–56%). Median duration of response was 2.1 months (95% CI = 0.2–4 months; range = 1.9–10.3 months). Median progression-free survival was 4.1 months (95% CI =1.8–6.4 months) and median overall survival was 9.9 months (95% CI = 4.8–15 months).
Among the 14 patients with epithelial ovarian cancer, 5 had a partial response and 3 had stable disease ≥ 6 months, yielding an objective response rate of 36% (95% CI = 13%–65%) and an objective response/stable disease ≥ 6 months rate of 57% (95% CI = 29%–82%). Median duration of response was 6.3 months (95% CI = 1.6–11 months). Median progression-free survival was 6.3 months (95% CI = 2.4–10.2 months), and median overall survival was 14.9 months (95% CI = 8.9–20.9 months).
Adverse Events
Treatment-related grade ≥ 3 adverse events occurred in 18 patients (60%), including anemia (20%), decreased neutrophils (17%), diarrhea (17%), decreased platelets (13%), nausea (13%), fatigue (10%), decreased white blood cells (10%), and sepsis (7%); acute kidney failure and thromboembolic events occurred in 3% each. Adverse events led to discontinuation of treatment in two patients. There were no treatment-related deaths.
The investigators concluded, “Adavosertib monotherapy demonstrates a manageable toxicity profile and promising clinical activity in refractory solid tumors harboring CCNE1 amplification, especially in epithelial ovarian cancer. Further study of adavosertib, alone or in combination with other therapeutic agents, in CCNE1-amplified epithelial ovarian cancer is warranted.”
Siqing Fu, MD, PhD, of the Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
