Adavosertib Monotherapy Demonstrated Clinical Activity in Women With Uterine Serous Carcinoma

The objective of the study was to analyze whether USC would be uniquely sensitive to further interference of cell cycle regulation by Wee1 inhibition.

Adavosertib monotherapy demonstrated clinical activity in women with uterine serous carcinoma (USC) with a preliminary response rate of 30%, according to a study presented via the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer. However, further studies in this patient population are necessary, according to the researchers.

The objective of the study was to analyze whether USC would be uniquely sensitive to further interference of cell cycle regulation by Wee1 inhibition.

“These are pills that are specifically detected to a specific type of uterine cancer,” said study author Susana Campos, MD, MPH, from the Dana-Farber Cancer Institute, in an interview with Pharmacy Times®. “Since this is a less frequent kind of cancer, the histology is a bit more aggressive.”

The study authors evaluated women with recurrent USC, including any women with cancers with any component assessed as serous. Patients were required to have had at least 1 prior platinum-based chemotherapy regimen. The patients with microsatellite instability-high (MSI-H)/mismatch repair deficiency (MMRd) disease were required to have already received prior therapy with a PD1/PDL1 therapy or to be ineligible for such therapy.

There was not a limit on the number of prior lines patients could have received and all patients were required to have RECIST measurable disease.

Patients were given 300 mg of adavosertib per day on days 1 through 5 and 8 through 12 of a 21-day cycle. In a total accrual of 35 patients, if at least 4 patients had confirmed response or 8 patients were progression-free at 6 months (PFS6), the trial would be considered positive with an alpha of 10% and a beta of 15% to detect coprimary endpoints of at least 20% overall response rate (ORR) or a 30% PFS6 rate.

Twenty-seven patients were enrolled in the study between October 11, 2018, and August 20, 2019, with a median follow-up of 3.5 months. The median number of prior lines was 3, and as of August 20, 2019, 21 patients were evaluable for response.

In these patients, 6 confirmed responses were observed, for an ORR of 30% with 1 additional patient having an unconfirmed response. The most frequent adverse events (AEs) observed included anemia, diarrhea, nausea, and fatigue. Frequently observed grade 3 or higher AEs included anemia, neutropenia, and syncope.

One of the most significant findings from the study for patients with USC was the high response rate, according to Campos.

“Patients have seen a complete response and it has been monumental,” Campos said in an interview with Pharmacy Times®. “Even with nausea or [gastrointestinal] distress as [AEs], patients tolerated [the drug] reasonably well.”

REFERENCE

Liu JF, Tayob N, Campos SM, et al. A phase II trial of the Wee1 inhibitor adavosertib (AZD1775) in recurrent uterine serous carcinoma. SGO 2020. https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/15031. Presented March 28, 2020. Accessed April 7, 2020.