Dr Silverstein on the Efficacy of Abemaciclib and Hormonal Therapy in Recurrent Ovarian and Endometrial Cancer

“CDK4/6 inhibitors with hormonal therapy are on the NCCN guidelines for endometrial cancer. However, in low-grade serous [ovarian cancer], they are not, and we saw with our study—and one other study that has been published—significant disease control. Our hope is that more patients with low-grade serous [ovarian cancer] can have access to these novel therapies.”

Jordyn Silverstein, MD, MSc, a hematology/oncology fellow and clinical instructor in the Division of Hematology/Oncology at the University of California, Los Angeles (UCLA), discussed updated efficacy, safety, and biomarker findings from a phase 2 trial (NCT04469764) of abemaciclib (Verzenio) plus physician’s choice hormonal therapy in patients with recurrent estrogen receptor (ER)–positive endometrial cancer and low-grade serous ovarian cancer (LGSOC).

The trial, which also included a third cohort of patients with high-grade serous ovarian cancer (HGSOC) selected for CDK4/6 pathway activation features, enrolled 43 patients: 21 with ER-positive endometrial cancer, 14 with LGSOC, and 8 with HGSOC who received abemaciclib at 150 mg twice daily plus hormonal therapy, most often letrozole (n = 37), regardless of prior treatment line.

In the ER-positive endometrial cancer cohort, the 24-week progression-free survival (PFS) rate was 56% (95% CI, 35%-78%) and the median PFS was 9.0 months (95% CI, 2.4-11.2), with a clinical benefit rate (CBR) of 63% and an objective response rate of 21%, Silverstein reported. Benefit was longest among patients whose tumors had no specific molecular profile (NSMP; n = 13), with median PFS of 10.4 months (95% CI, 2.4-21.0) in that subgroup, according to Silverstein.

In the LGSOC cohort, the combination produced durable disease control regardless of KRAS mutation status, with a median PFS of 17.5 months (95% CI, 3.5-not reached) and a CBR of 79%, Silverstein said. Four in 14 patients with LGSOC (28%) remained on treatment for more than 3 years as of the December 2025 data cutoff, she noted.

Silverstein added that CDK4/6 inhibitors plus hormonal therapy are already recommended in NCCN guidelines for endometrial cancer but not for LGSOC, and said she hopes these findings help expand access to the combination for patients with LGSOC.