Author(s): Feriel Boumedien, Jean-Philippe Adam, Khalid Akkour, Nathalie LeTarte, Diane M. Provencher; Faculty of Medicine, Université de Montreal, Montreal, QC, Canada; Centre hospitalier de l’Université de Montréal (CHUM), Montreal, QC, Canada; Centre hospitalier de l’Université de Montréal, Montréal (Québec),, Montreal, QC, Canada; CHUM, Montreal, QC, Canada; Centre hospitalier de l'Université de Montréal, Montreal, QC, CanadaAbstract Disclosures
Abstract:
Background: Trabectedin is approved in Canada since 2010 in combination with liposomal doxorubicin for platinum-sensitive ROC in patients who are not expected to benefit, are ineligible or not willing to receive retreatment with platinum-based chemotherapy. In 2012, due to a shortage of liposomal doxorubicin, single agent trabectedin was proposed to patients with ROC. The aim of this study was to evaluate the efficacy and tolerability of trabectedin in this context.
Methods: This retrospective IRB approved study included all patients who received trabectedin for ROC between January 1st 2012 and June 30th 2014 at the CHUM.
This study was not funded.The primary outcome was progression free survival (PFS) based on CA-125 and clinical exam. We also evaluated overall survival (OS), response rate and toxicities (CTCAE v4.0). PFS and OS were estimated by Kaplan-Meier method.
Results: A total of 25 evaluable patients with a median age of 59 years received trabectedin 1.3 mg/m2 I.V. in 3 hours every 3 weeks in 3rd or 4th line (36%), 5th or 6th line (36%) and ≥ 7 lines (28%). Among the patients, 60% were platinum-sensitive and 40% platinum-resistant.
The median number of cycles received was 5 (range 1-16 cycles) for a total of 130 cycles.
" Complete Response " (CR), partial response (PR), stable disease (SD) and progression occurred in 16%, 20%, 24% and 40% of patients respectively.
The median PFS was 3.7 months (95% CI 1.9-5.6). In patients with a response (CR, PR, SD), the median PFS was 4.9 vs 0.8 months (p < 0.001). Death occurred in 15 patients (60%).
The median OS was 16.2 months. The Cox model reported that response to treatment is the only variable influencing the PFS and the OS (p < 0.001), but not the platinum status or the number of previous lines received. Grade 3 or 4 toxicities include: neutropenia (8%), febrile neutropenia (4%) and muscle weakness (4%). Dose reduction was required in 4 patients for hepatic and hematologic toxicities. No death was attributable to toxicities.
Conclusions: Our results demonstrate that trabectedin has an interesting efficacy as a single agent in heavily treated ROC patients. At a dose of 1.3 mg/m2 every 3 weeks, trabectedin is well tolerated with few adverse events.