Optimising the treatment of the partially platinum-sensitive relapsed ovarian cancer patient

The choice of second-line chemotherapy in patients with recurrent ovarian cancer (ROC) is complex, with several factors to be considered, the most important of which is the length of the platinum-free treatment interval (PFI). Recently ROC patients have been further stratified into platinum sensitive (PS), partially platinum sensitive (PPS) and platinum resistant (PR) subgroups depending on the length of the PFI. Response to second-line therapy, progression-free survival (PFS) and overall survival (OS) are linked to the PFI, all of them improving as the PFI increases. Consequently, there is increasing interest in PFI extension strategies with platinum-free therapeutic options. Such strategies are currently being studied in patients with partially platinum-sensitive disease (PFI 6-12 months), as the treatment of these patients remains clinically challenging. A non-platinum option, trabectedin + pegylated liposomal doxorubicin (PLD) combination, has been evaluated in ROC patients in the pivotal phase III OVA-301 study. The OVA-301 study differed from previous trials in the same setting as it included only patients who were not expected to benefit from or who were ineligible for or who were unwilling to receive re-treatment with platinum-based chemotherapy, including those with PPS and PR disease. Subset analysis of patients with PPS disease in OVA-301 showed that the trabectedin + PLD combination significantly improved PFS compared with PLD alone; median PFS 7.4 versus 5.5 months, p=0.0152. Final survival data from the same subset of patients, showed that trabectedin + PLD also achieved a significant 36% decrease in the risk of death compared with PLD alone (HR=0.64; 95% CI, 0.47-0.88; p=0.0027). Median overall survival (OS) was 22.4 months in the trabectedin + PLD arm versus 16.4 months in the PLD arm. This represents a statistically significant 6-month improvement in median OS in patients treated with trabectedin + PLD compared to those treated with PLD alone.