Platinum rechallenge (PtRc) in platinum-resistant epithelial ovarian cancer (PR-EOC) patients: Is platinum-resistance a static or a dynamic status? (485)

Abstract

<b>Objectives:</b> Epithelial ovarian cancer (EOC) is the leading cause of death due to gynecological malignancies in the developed world. Platinum-free interval (PFI) ≥6 months (m), an arbitrary temporal threshold, establishes platinum-based therapy as the cornerstone of therapy in the recurrent setting. However, the evolving therapeutic landscape of EOC enables us to consider pts either suitable or not suitable for further platinum therapy based on additional factors. Currently, a remarkable number of pts maintain a good performance status (PS) and may receive multiple treatment lines in the platinum-resistant setting. We aimed to explore the efficacy of Platinum rechallenge (PtRc) in pts considered not suitable for further platinum therapy based solely on PFI and identify clinical and molecular markers of response. <b>Methods:</b> Consecutive EOC pts treated at our institution from 2010 to 2020 were retrospectively reviewed using medical charts. PtRc candidates were those with PFI <6m after last platinum therapy and treated with non-platinum agents afterward for at least one year. Clinical and molecular data were evaluated, including <i>BRCA1/2</i> mutation status. Statistical analysis was done using R software 4.1.1. <b>Results:</b> Forty-three pts were analyzed. The median age of patients was 57 years (IQR: 50-63); 37 pts (86%) had a PS of ≤1.<i>BRCA1/2</i> mutations were identified in eight pts (18.6%). The median number of lines prior to PtRc was 5 (IQR: 4-6). The median PFI from the last platinum line was 25m (95% CI: 21.8-28.1). PtRc regimens included platinum doublets with paclitaxel (48.8%), PLD (36.6%), and gemcitabine (14.6%). The objective response rate (ORR) was 58.1% (all partial responses) with a disease-control rate of 80%. The median progression-free survival (mPFS) for the whole cohort was 6.7m (95% CI: 5.7-8.6). In the univariate analysis, pts with <i>BRCA1/2</i> mutation had longer mPFS compared to <i>BRCA</i>wild type (10.2 vs 6.51m; HR: 0.26 [95% CI: 0.09-0.75], p=0.01), and greater ORR (62.5% vs 52.8%, respectively, p=0.07). Earlier administration of PtRc was associated with increased mPFS (8.4m for <4 lines vs 5.5m for >4 lines; HR: 0.38 [95% CI: 0.19-0.76], p=0.01). While PFI, after the PtRc was 2.3m (95% CI: 1.9-3.6) compared to 4.4m (95% CI: 3.8-5] in the last platinum line, a 13.9% of pts, achieved a PFI of >6m after PtRc, three of which were <i>BRCA</i>- mutated and three were not. <b>Conclusions:</b> PtRc may still be an option in PR-EOC pts, especially in those who have received fewer lines of treatment in the resistant setting and harbor <i>BRCA1/2</i> mutations. Of note, 13.9% of pts had a PFI of >6 m after PtRC, indicating that platinum sensitivity is a dynamic status. Further investigation on biomarkers is needed to better select pts for PtRc.