Extending the platinum-free interval (PFI) following disease progression in ovarian cancer with a non-platinum agent does not improve outcomes over the standard practice of using a platinum-based chemotherapy (PBC), according to a prospective trial.
Most patients with ovarian cancer progress following surgery and a first-line PBC regimen. “Retreatment with PBC is possible—the effectiveness of treatment with PBC increases with a longer interval from the initial PBC treatment,” wrote study authors led by Sandro Pignata, MD, PhD, of the Istituto Nazionale dei Tumori in Naples, Italy. “The extension of PFI, intercalating a nonplatinum treatment, was hypothesized in 1999 as a strategy to increase the sensitivity of the disease to platinum treatment.”
The new MITO-8 trial was an open-label, prospective, randomized study that included 215 patients with ovarian cancer who had disease progression between 6 and 12 months after their last platinum treatment; the trial ended early due to slow enrollment. They were randomized to receive either a non-PBC followed by PBC at subsequent relapse, or to the reverse. The results were published in the October issue of the Journal of Clinical Oncology.
The PFI was effectively prolonged in the experimental arm of the trial, with a median of 7.8 months from randomization and 15.8 months from last platinum injection before study entry, compared with 0.01 months and 8 months, respectively, in the standard therapy arm.
There were a total of 72 deaths in the experimental group and 69 in the standard therapy group, for a median overall survival (OS) of 21.8 months and 24.5 months, respectively, yielding a hazard ratio (HR) of 1.38 (95% CI, 0.99–1.94; P = .06).
The median progression-free survival (PFS) after the two planned treatments was 12.8 months in the prolonged PFI group and 16.4 months in the standard therapy group, for an adjusted HR of 1.41 (95% CI, 1.04–1.92; P = .025).
An analysis of global health status and quality-of-life scores showed that the experimental arm resulted in significantly worse outcomes after 3 cycles of treatment (P = .003), but this effect disappeared after 6 cycles (P = .46). Rates of adverse events were similar between the groups.
“Prolongation of PFI in the MITO-8 trial did not produce any survival advantage for patients with partially platinum-sensitive ovarian cancer,” the authors concluded. Instead, both OS and PFS appeared worse when the second treatment with platinum-based chemotherapy is delayed. “It is also advisable that PBC be used as the control arm in future trials of new drugs in this setting.”