Abstract 16P
Background
Low-grade serous ovarian cancer (LGSC) is a rare ovarian cancer subtype that has distinctive genomic, histopathological and clinical characteristics, compared to the more common high-grade serous ovarian cancer (HGSC). Response to platinum-based chemotherapy, the mainstay of ovarian cancer treatment, is sub-optimal and outcomes for advanced LGSC can be poor. Additional treatment options are needed for LGSC, and non-platinum chemotherapy regimens have not been fully explored. Therefore, the aims of our study were to: 1. Assess real-world treatment and response patterns in LGSC; 2. Examine response to non-platinum agents in LGSC cell lines.
Methods
A LGSC cohort (n=99) with clinical data available, was identified from >4,000 patients recruited to the Australian Ovarian Cancer Study, GynBiobank and the INOVATe study. LGSC diagnoses were verified by stringent histopathological criteria and absence of TP53 mutations. Responses to non-platinum chemotherapy agents, including docetaxel and paclitaxel were assessed in eight patient-derived LGSC cell lines: HOC7, HCC5075, MPSC1, WMOV24, AOCS2, WMINV10, WMINV13 and HO433; by a cell viability assay.
Results
More than 12 different chemotherapy drugs were used in the clinical management of LGSC patients (1992-2017), either as single agent or in combination. The most common single agent chemotherapies used were liposomal doxorubicin (n=19), carboplatin (n=11), paclitaxel (n=9) and docetaxel (n=7). In patients with an evaluable treatment response, highest response rates were seen to the taxanes docetaxel (2/3, 67%) and paclitaxel (2/7, 28.5%). Three LGSC lines (MPSC1, HCC5075 and HOC7) were relatively sensitive to docetaxel (IC50 1.8-3.8 nM), and of these two were also sensitive to paclitaxel (HCC5075, HOC7) (IC50 1.5-2 nM). There was no association between taxane sensitivity in LGSC cell lines and MAPK pathway gene alterations, which is the most prevalent molecular feature of LGSC, found in ∼50% of cases.
Conclusions
Preliminary results suggest that taxanes could be an effective chemotherapeutic option for LGSC. However, these results need to be validated in larger cohorts, and biomarkers predictive of response are needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Westmead Charitable Trust ECR Medical Clinician-Researcher Grant 2021, Cancer Council NSW (RG-15-23) and Cancer Australia (APP1142697). The INOVATe study has received funding from the Cancer Institute NSW (Translational Program Grant 14/TPG/1-15), the Cancer Council NSW (Translational Program Grant TPG 20-01) and the University of Sydney.
Disclosure
All authors have declared no conflicts of interest.