The Changing Landscape of Therapeutic Strategies for Recurrent Ovarian Cancer

Klaus H Baumann; Uwe Wagner; Andreas du Bois

Disclosures

Future Oncol. 2012;8(9):1135-1147. 

In This Article

Partially Platinum-sensitive Ovarian Cancer

Patients experiencing ovarian cancer recurrence >6 months and ≤12 months after prior platinum-based first-line chemotherapy are classified as partially platinum-sensitive.[3] These women benefit from platinum-based reinduction chemotherapy. The therapeutic effect, however, is lower than in women characterized as platinum-sensitive.[23] The OVA-301 Phase III trial tested the efficacy of trabectedin and PLD versus PLD alone in recurrent ovarian cancer.[35] A subgroup analysis included 214 women with partially platinum-sensitive recurrent ovarian cancer. Trabectedin in combination with PLD resulted in a 35% risk reduction of disease progression or death (HR: 0.65; 95% CI: 0.45–0.92; p = 0.0152; median PFS: 7.4 vs 5.5 months). Risk of death was reduced by 41% (HR: 0.59; 95% CI: 0.43–0.82; p = 0.0015; median overall survival: 23.0 vs 17.1 months).[35] These results provide evidence to prolong the platinum-free interval in this patient population by a nonplatinum chemotherapy.[36] Subsequently, platinum-based reinduction chemotherapy for third-line treatment might be selected. Two important clinical trials are ongoing to investigate the concept of prolonging the platinum-free interval in partially platinum-sensitive ovarian cancer (Figure 1). The objective of the multicenter, randomized Phase III INOVATYON trial is to demonstrate superiority, in terms of prolonged survival, of trabectedin (1.1 mg/m2) and PLD (PLD 30 mg/m2) versus carboplatin (AUC 5) and PLD (30 mg/m2).[37] The Mito-8 trial aims to test the hypothesis that the artificial prolongation of the platinum-free interval with a nonplatinum treatment will improve the effectiveness of overall therapy in patients with ovarian cancer progression occurring 6–12 months after first-line treatment with a platinum derivative.[38] Patients will be randomized to stealth liposomal doxorubicin followed at a later progression by carboplatin and paclitaxel, or to carboplatin and paclitaxel followed at a later progression by stealth liposomal doxorubicin.[103] Both trials are currently affected by the shortage of PLD, but are expected to resume enrollment.

A subgroup analysis of 344 women with partially platinum-sensitive recurrent ovarian cancer treated within the CALYPSO trial showed that carboplatin plus PLD has a more favorable risk–benefit profile than carboplatin plus paclitaxel.[39] The HR for PFS was 0.73 (95% CI: 0.58–0.90; p = 0.004 for superiority; median PFS: 9.4 [carboplatin plus PLD] and 8.8 months [carboplatin plus paclitaxel]) in favor of carboplatin plus PLD.[39]

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