Joshua G. Cohen, MD, Associate Clinical Professor in the Department of Surgery and Medical Director of the Orange County Gynecologic Cancer Program at City of Hope, Orange County, California, shared his thoughts on the ADAGIO trial with The ASCO Post. He noted that uterine serous carcinoma—the population studied in the phase IIb ADAGIO trial, for which the Wee1 kinase inhibitor adavosertib was evaluated—is an aggressive tumor with a high risk for recurrence and shorter survival than endometrioid endometrial cancers. Adavosertib has shown activity in solid tumors harboring CCNE1 amplification, he added.
“The analysis of the 109 patients presented by Dr. Joyce Liu demonstrated that adavosertib does have activity against uterine serous carcinoma, with an overall response rate of 26% in 104 evaluable patients,” he said. However, 97% of patients had a treatment-related adverse event, of which 60.6% were grade ≥ 3, he noted.
Joshua G. Cohen, MD
“The high rate of treatment-related adverse events may be due, in part, to a heavily pretreated population, with a median of three prior lines of therapy. Due to treatment history, the patients in this study may have been at higher risk for bone marrow toxicity and cumulative toxicity,” Dr. Cohen suggested.
“Further use of this drug in this patient population may require modification of the initial dose used because of significant toxicity. Ongoing clinical evaluation of adavosertib with or without olaparib in patients with recurrent ovarian cancer has shown treatment response but with similarly high rates of treatment-related adverse events. Because of the narrow therapeutic window, biomarkers are needed to better identify who will benefit most from this drug. Given the activity seen with adavosertib in solid tumors with CCNE1 amplification, those patients with uterine serous carcinoma who have tumor CCNE1 amplification may be a future population to focus on,” Dr. Cohen said.
DISCLOSURE: Dr. Cohen reported no conflicts of interest.
The oral, small-molecule Wee1 kinase inhibitor adavosertib was clinically active but not well tolerated by more than half the patients with recurrent or persistent uterine serous carcinoma in the phase IIb ADAGIO trial. The findings were reported at the Society of Gynecologic Oncology (SGO) 2023...