A pilot translational study of neoadjuvant fulvestrant plus abemaciclib in women with advanced low-grade serous carcinoma.

Low-grade serous carcinoma of the ovary (LGSOC) is relatively resistant to chemotherapy. Given its biological parallels to hormone receptor-positive breast cancer, including responsiveness to anti-estrogen therapies, we conducted a pilot phase II study to assess clinical benefit of neoadjuvant fulvestrant and abemaciclib in women with advanced, unresectable LGSOC (NCT03531645). Imaging assessments were performed every 8 weeks until resectable. The primary endpoint was clinical benefit rate (CBR). Exploratory objectives included evaluation of safety profile, accessing biomarkers related to clinical benefit, and description of tumor phenotypic changes. Fifteen patients were enrolled and evaluable for efficacy. CBR was 100%, with 1/15 patients (7%) achieving complete response (CR), 8/15 patients (53%) achieving partial response (PR), and 6/15 (40%) exhibiting stable disease (SD). Interval cytoreductive surgery (ICS) was performed in 9 patients (60%), with 7 (78%) achieving complete or optimal resection. Fourteen tumor samples underwent transcriptomic and proteomic profiling. Tumors from long-term survivors showed significantly higher baseline expression of cell-cycle-related programs and estrogen signaling-related genes, both suppressed upon treatment. Neoadjuvant fulvestrant and abemaciclib was well tolerated, achieved high response rates, and enabled optimal surgical resection in most patients. Tumor proliferative activity and estrogen signaling dependency may predict therapy response.