Trabectedin plus pegylated liposomal doxorubicin in the treatment of patients with partially platinum-sensitive ovarian cancer: current evidence and future perspectives.

The effectiveness of platinum re-treatment in relapsed ovarian cancer depends on relapse-free/treatment-free intervals. Platinum agents can be effectively readministered to platinum-sensitive patients (relapsing >12 months after platinum), but efficacy is lower in partially platinum-sensitive (PPS) disease (relapsing 6-12 months after platinum). There is no clear standard treatment challenging PPS patients. Survival data in this subset with chemotherapy combinations such as pegylated liposomal doxorubicin (PLD) plus carboplatin or gemcitabine plus PLD are available from phase II trials ranging from 16 to 21 months. Recent results from OVA-301 phase III randomized trial evaluating trabectedin plus PLD showed the longest median overall survival ever reported in PPS patients (23 months). Subsequent chemotherapy (including platinum-based regimens) was administered later and survival in patients receiving third-line platinum was longer in patients treated with trabectedin plus PLD compared with those treated with PLD alone. These results suggest that prolonging platinum-free interval (PFI) with an effective non-platinum regimen improves outcome with subsequent third-line platinum treatment. An ongoing phase III trial (INOVATYON) aims to demonstrate if the results observed with trabectedin plus PLD in PPS patients are due to PFI extension, and if PFI extension with non-platinum combination prolongs response to subsequent platinum and survival in this population.