Adavosertib is active but not well tolerated in patients with recurrent or persistent uterine serous carcinoma (USC), according to research presented at the 2023 SGO Annual Meeting on Women’s Cancer.
“Adavosertib showed antitumor activity in patients with advanced, recurrent or persistent USC,” said study presenter Joyce F Liu, MD, of Dana-Farber Cancer Institute in Boston. “Adavosertib dosed at 300 mg daily, however, was not well tolerated, despite toxicity management in this heavily pretreated USC population.”
Dr Liu and colleagues tested adavosertib in the phase 2b ADAGIO trial (ClinicalTrials.gov Identifier: NCT04590248). The trial enrolled 109 patients with recurrent or persistent USC who had previously received 1 or more platinum-based chemotherapies.
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At baseline, the patients’ mean age was 68.8 years, 84.4% were White, and 77.1% had pure serous histology. Patients had received a median of 3 prior lines of therapy. All patients had received platinum compounds, 98.2% had received taxanes, and 28.4% had received PD-1/PD-L1 inhibitors.
On study, the patients received oral adavosertib at 300 mg daily on days 1-5 and 8-12 of a 21-day cycle. At the data cutoff, 7 patients were still on therapy. The reasons for treatment discontinuation were disease progression (n=64), adverse events (n=19), patient decision (n=10), investigator decision (n=2), death (n=1), and other reasons (n=6).
The study’s primary endpoint was objective response rate (ORR) by blinded independent central review. In 104 evaluable patients, the ORR was 26.0%. One patient had a complete response, 26 had a partial response, and 42 had stable disease. The median duration of response was 4.7 months.
The ORR by investigator assessment, for which all 109 patients were evaluable, was 21.1%. Two patients had a complete response, 21 had a partial response, and 52 had stable disease. The median duration of response was 5.6 months.
All 109 patients were evaluable for progression-free survival (PFS) and overall survival (OS). The median PFS was 2.8 months, and the median OS was 9.6 months.
In a subgroup analysis of all 109 patients, outcomes were superior among patients who had not previously received PD-1/PD-L1 inhibitors. The ORR was 28.9% in the PD-1/PD-L1-naïve cohort and 17.9% in the PD-1/PD-L1-exposed cohort.
The median PFS was 3.4 months in the PD-1/PD-L1-naïve cohort and 2.8 months in the PD-1/PD-L1-exposed cohort. The median OS was 11.4 months and 8.7 months, respectively.
Overall, 97.2% of patients had any treatment-related adverse events (TRAEs), and 60.6% had grade 3 or higher TRAEs. Fifty-five percent of patients had TRAEs leading to dose reductions, 56.9% had TRAEs leading to dose interruptions, and 14.7% had TRAEs leading to treatment discontinuation. The rate of fatal TRAEs was 0.9%.
The most common TRAEs of grade 3 or higher were neutropenia (21.1%), fatigue (13.8%), thrombocytopenia (8.3%), anemia (8.3%), and diarrhea (8.3%).
“Overall, our findings indicate that while wee1 inhibition results in antitumor activity in USC and may remain a viable treatment target, the therapeutic window for adavosertib was narrow,” Dr Liu concluded.
Disclosures: This research was supported by AstraZeneca and Parexel. Dr Liu disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Genentech/Roche, GlaxoSmithKline, Regeneron, 2X Oncology, Acetylon Pharmacuetical, Agenus, Aravivie, Arch Oncology, Boston Biomedical, CytomX Therapeutics, Impact Therapeutics, Surface Oncology, Vegeo Therapeutics, and Zentalis.
Reference
Liu JF, Colombo N, Oza A, et al. ADAGIO: A phase IIb, open-label, single-arm, multicenter study assessing the efficacy and safety of adavosertib (AZD1775) as treatment for recurrent or persistent uterine serous carcinoma. SGO 2023. March 25-28, 2023.
