Site Editor
Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Friday, October 31, 2025
The absence of effective strategies to diagnose ovarian cancer in the early stages is a significant factor contributing to the disease’s high mortality rates. In a recent study published in JCO Precision Oncology, lead author Chiara Maura Ciniselli, PhD, of the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, and colleagues, investigated how real-world clinicogenomic data can be used to identify molecular targets and bridge treatment gaps for patients with high-grade serous ovarian cancer (HGSOC) the most common—and most aggressive—subtype of ovarian cancer.
Study Details
The investigators leveraged the Flatiron Health–Foundation Medicine Clinicogenomic Database, encompassing data from approximately 280 U.S. cancer centers, to evaluate the molecular diversity of HGSOC and assess the clinical impact of comprehensive genomic profiling (CGP). The authors aimed to determine how CGP could uncover new therapeutic avenues beyond established biomarkers such as BRCA1/2 mutations and homologous recombination deficiency (HRD).
The retrospective observational study included 856 patients diagnosed with HGSOC between January 2011 and September 2023. Among these, 439 patients were selected for clinical analysis, with the cohort categorized into no surgery (n = 74), interval surgery (n = 157), and upfront surgery groups (n = 208). A total of 78% of the patients had stage III to IV disease.
Key Results
CGP detected BRCA1 and BRCA2 mutations in 11.7% and 6.5% of patients, respectively. Beyond these, several potentially actionable genomic alterations were also identified, notably CCNE1 (16%), FGFR1–4 (6.5%), PIK3CA (3.9%), TP53 Y220C (3.7%), ERBB2 (3.5%), CDK12 (2.3%), ARID1A (2.2%), KRAS (2.1%), and BRAF (1%). As the authors note, “CCNE1 amplification is associated with resistance to platinum-based chemotherapy and poor prognosis, and thus primarily represents a potential target for therapeutic intervention.” In addition, CCNE1 amplification appeared to be mutually exclusive with BRCA1/2 mutations, consistent with earlier genomic studies. Loss-of-heterozygosity (LOH)—a surrogate for HRD—was present in close to 33% of cases, but its prognostic value was limited in this cohort.
Patients with BRCA-mutated tumors showed superior event-free survival (EFS) relative to wild-type cases, reflecting the benefit of PARP inhibitor therapy. Patients treated with PARP inhibitors had significantly improved EFS (hazard ratio = 1.77, 95% confidence interval = 1.21–2.58). Among BRCA-wild-type, LOH-negative patients, who are typically ineligible for PARP inhibitors, CGP revealed that 99 patients (48%) harbored other potentially targetable genomic alterations.
Conclusions
This study highlights the ability of CGP to delineate the molecular complexity of HGSOC and identify actionable alterations that extend beyond HRD and BRCA1/2 mutations. Using real-world analysis, the authors demonstrated that integrating CGP into standard clinical practice can substantially expand therapeutic decision-making, especially through the use of institutional molecular tumor boards.
“Overall, our study provides evidence that CGP significantly improves the identification of molecular targets in HGSOC, supporting its importance in the clinical practice to provide patients with more therapeutic options,” they stated.
Disclosure: For full disclosures of all study authors, visit ascopubs.org.
