Prolonging the platinum-free interval (PFI) with trabectedin to allow retreatment with platinum-based chemotherapy in patients with platinum-refractory and -resistant recurrent ovarian cancer (PROC).

Abstract

e16543 Background: Dose-dense therapy and administration of sequential non-platinum agents in PROC plays a role in reverting platinum-resistance and may improve the prognosis of such patients over years (Bamias A, 2013). The PFI extension is one of the current strategies to improve survival in partially platinum-sensitive (PPS) ROC, with a PFI 6-12 months (Poveda A, 2011). Trabectedin is a minor groove DNA-binder, which may play a role in reverting platinum resistance in patients with PROC and PPS ROC. Methods: Trabectedin 1.1-1.5 mg/m2as single agent was given as a 3-h infusion every 3 weeks with antiemetic and steroid premedication. Tumor response was assessed every 12 weeks. Results: Overall, 27 patients (24 with PROC and 3 with PPS ROC) treated from 2003 to 2013 in a single institution were included in the analysis. The patients had a median age of 63 years (range 45-81), most had serous-papillary (67%), clear-cell (11%), endometrioid (7%) and other (15%) histological subtypes and received a median of 5 prior chemotherapy lines (range: 1-9), 89% of whom also received other non-platinum agents. A median of 4.9 trabectedin cycles (range 1-14) was given. The overall response rate (ORR) was 15%, with a median duration of response of 16.5 weeks (range 5.86-44.43), while 41% of patients achieved stable disease (SD) lasting ≥4 months as best response. Thirteen of 27 patients were retreated with platinum-based chemotherapy after progression with trabectedin treatment. The ORR to platinum retreatment was 54% (n = 7) and SD was achieved in 8% (n = 1) of these patients, for an overall clinical benefit of 61%. Conclusions: Intercalation of a non-platinum therapy with trabectedin prior to subsequent platinum rechallenge may contribute to prolong PFI and to re-sensitize the patients with PROC and PPS ROC to further platinum-based therapies leading to a significant clinical benefit. Further prospective studies are warranted to determine the contribution of sequential treatments with trabectedin in patients with PROC and PPS ROC.