Gene expression and mutation profiles in advanced-stage epithelial ovarian cancer (EOC)

Purpose: This open-label, investigator-initiated, phase II study was conducted to evaluate the safety, survival and neoadjuvant outcomes of NAC combined with dual immune checkpoint inhibitors in advanced-stage EOC. Patients and methods: Between June 2019 and July 2021, 45 patients with unresectable stage III-IV EOC were enrolled. The patients received three cycles of NAC combined with durvalumab and tremelimumab. All patients underwent interval debulking surgery and received three cycles of durvalumab and adjuvant chemotherapy, followed by 12 cycles of durvalumab as maintenance therapy. The primary endpoint was the 12-month progression-free survival (PFS) rate; the secondary endpoints were the objective response rate (ORR) after NAC, a chemotherapy response score (CRS), pathologic complete response (pCR), overall survival (OS), and safety. The pre-planned exploratory analyses assessed the lymphocyte infiltration, PD-L1 expression, and genomic profiles of pre-treatment tumors. Pretreatment tumors samples from fresh-frozen tissue were obtained for whole-transcriptome sequencing and whole-exome sequencing. RNA and DNA samples were sequenced on HiSeq 2500 sequencing platform. For RNA-seq, sequencing reads were aligned to the human reference genome (GRCh37) by using STAR aligner. Expected counts of reads mapped into genes were estimated and transformed into TPM values by RSEM. For whole exome sequencing, sequenced reads were aligned to the reference human genome (GRCh37) using the Burrows-Wheeler Aligner (BWA). After pre-processing using the Genome Analysis Toolkit (GATK), variants were called by Mutect2. *************************************************************** Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access. ***************************************************************