In the phase IIb ADAGIO trial, reported in the Journal of Clinical Oncology, Liu et al found that the Wee1 inhibitor adavosertib showed some activity in patients with recurrent or persistent uterine serous carcinoma. However, its use was associated with high toxicity rates.
Study Details
In the trial, 104 evaluable patients from sites in Canada, France, Germany, Italy, Spain, and the United States who had previously received platinum-based chemotherapy were enrolled between December 2020 and November 2021. Patients received adavosertib at 300 mg once daily on days 1 to 5 and 8 to 12 of 21-day cycles. The primary outcome measure was objective response on blinded independent central review.
Key Findings
Among the 104 evaluable patients, objective responses were observed in 27 (26.0%, 95% confidence interval [CI] = 17.9%–35.5%), with a complete response in 1. The median duration of response was 4.7 months (95% CI = 3.8–8.3 months). The median progression-free survival was 2.8 months (95% CI = 2.6–3.9 months).
Biomarker analysis in archival tissue from 77 patients showed no single alteration predictive of objective response to adavosertib. Trends in higher likelihood of response were associated with CCNE1 amplification (40%) and high cyclin E1 protein expression (32%).
Treatment-related adverse events of any grade occurred in 97.2% of patients, most commonly diarrhea (59.6%), nausea (59.6%), and anemia (58.7%). Grade ≥ 3 treatment-related adverse events were reported in 60.6%, most commonly neutropenia (21.1%) and fatigue (13.8%). Treatment-related adverse events led to discontinuation of treatment in 14.7%.
Adavosertib is no longer under clinical development. However, results from this trial may help to inform development of other Wee1 inhibitors.
The investigators concluded: “Adavosertib showed some antitumor activity in patients with recurrent/persistent [uterine serous carcinoma]. However, at 300 mg once daily dosing, it was not well tolerated in this population. Exploratory biomarker studies suggest CCNE1/cyclin E1 expression may enrich for response to Wee1 inhibition in [uterine serous carcinoma].”
Joyce F. Liu, MD, MPH, of the Department of Medical Oncology, Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
