A Pilot Translational Study of Neoadjuvant Fulvestrant plus Abemaciclib in Women with Advanced Low-Grade Serous Carcinoma
Code repository for GeoMx DSP WTA part of the paper. Raw data were in the GEO database. Source data of images were in supplementary data in the publication.
The raw data of GeoMx DSP WTA have been deposited in the Gene Expression Ominibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE292946.
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 study to assess clinical benefit of neoadjuvant fulvestrant and abemaciclib in women with advanced, unresectable LGSOC. Imaging assessments were performed every 8 weeks until resectable. The primary endpoint was clinical benefit rate (CBR). Fourteen tumor samples from 8 patients underwent molecular profiling via RNA sequencing, reverse phase protein array, immunohistochemistry, and GeoMx digital spatial profiling. Fifteen patients were enrolled and evaluable for efficacy. CBR was 100%, with 9/15 patients (60%) achieving partial response (PR), and 6 (40%) exhibiting stable disease (SD). Interval cytoreductive surgery (ICS) was performed in 9 patients (60%), with 7 (78%) achieving complete or optimal resection. Tumors from long-term survivors showed significantly higher baseline expression of cell-cycle-related transcriptional programs and estrogen signaling pathways, both of which were suppressed by treatment. Neoadjuvant fulvestrant and abemaciclib was well tolerated, achieved unprecedented response rates, and enabled optimal surgical resection in the majority of patients. Tumor proliferative activity and estrogen signaling dependency may predict response to this combination therapy.
This study was conducted in collaboration with Drs. Cara Haymaker and Luisa M. Solis Soto from the Translational Molecular Pathology Immunoprofiling Laboratory (TMP-IL) at the University of Texas MD Anderson Cancer Center.