Platinum-based chemotherapy for patients with progressing ovarian cancer is more effective with a longer time interval from previous Platinum treatment ( Platinum-free interval ).
In 1999, it was hypothesized that prolonging Platinum-free interval with single-agent non-Platinum-based chemotherapy ( NPBC ) may offer a strategy to improve overall outcome.
MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested.
MITO-8 is an open-label, prospective, randomized, superiority trial.
Patients with ovarian cancer who experienced disease progression 6 to 12 months after their last Platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by Platinum-based chemotherapy at subsequent relapse or the standard reverse treatment sequence.
Overall survival was the primary end point.
Two hundred fifteen patients were enrolled ( standard arm [ n = 108 ]; experimental arm [ n = 107 ] ).
The trial ended before planned because of slow enrollment.
Platinum-free interval was prolonged in the experimental arm ( median, 7.8 vs 0.01 months ).
There was no overall survival benefit in the experimental arm ( median, 21.8 vs 24.5 months; hazard ratio, HR=1.38; 95% CI, 0.99 to 1.94; P = 0.06 ).
Progression-free survival after the sequence was significantly shorter in the experimental arm ( median, 12.8 vs 16.4 months; HR=1.41; 95% CI, 1.04 to 1.92; P = 0.025 ).
Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects.
In conclusion, MITO-8 supports the recommendation that Platinum-based chemotherapy not be delayed in favor of an non-Platinum-based chemotherapy in patients with partially Platinum-sensitive ovarian cancer.
Platinum-based chemotherapy should be used as a control arm in future trials of new drugs in this setting. ( Xagena )
Pignata S et al, J Clin Oncol 2017;35:3347-3353