Does Platinum-Free Interval Prolongation Improve Outcomes in Progressive Ovarian Cancer?

Submitted by admin5 on Fri, 10/13/2017 - 14:31

A recent study assessed the hypothesis that prolonging the platinum-free interval with platinum-free chemotherapy may offer improved outcomes in patients with progressing ovarian cancer, published in the Journal of Clinical Oncology (October 2017;35[29]:3347-3353).

Prior studies have demonstrated that platinum-based chemotherapy for patients with progressing ovarian cancer is most effective when taken in conjunction with a longer time interval from the previous platinum-based treatment. In 1999, researchers hypothesized that prolonging the platinum-free interval with a single-agent non-platinum-based chemotherapy may offer an option to improve overall outcomes. This strategy is often used in clinical practice, though it has yet to be prospectively studied.

Sandro Pignata, MD, PhD, IRCCS National Cancer Institute (Naples, Italy), and colleagues conducted an open-label, prospective, randomized, superiority trial (MITO-8) to verify this hypothesis. A total of 250 patients were enrolled with ovarian cancer who experienced progression 6-12 months after their last platinum treatment. Patients were assigned (1:1) to the experimental arm (single-agent non-platinum-based chemotherapy followed by platinum-based chemotherapy; n = 107) or the standard arm (reverse treatment sequence; n = 108). The median platinum-free interval was extended in patients in the experimental arm (7.80 months vs 0.01 months for those in the standard arm).

The primary endpoint of the trial was overall survival (OS). Researchers acknowledged that they had to end the trial early due to enrollment issues.

Results of the analysis showed that there was no significant OS benefit in patients in the experimental arm compared with the standard arm (median OS, 21.8 vs 24.5, respectively; HR, 1.38; 95% CI, 0.99-1.94; P = .06). Furthermore, progression-free survival (PFS) was definitively shorter in patients in the experimental arm (median PFS, 12.8 vs 16.4 months, respectively; HR, 1.41; 95% CI, 1.04-1.92; P = .025).


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Researchers also noted that global quality of life changes after three treatment cycles favored patients in the standard arm. Only minor discrepancies were observed between patients in the treatment arms in the incidence of adverse events.

In their concluding remarks, researchers asserted that platinum-based chemotherapy should not be delayed in favor of non-platinum-based chemotherapy in patients with partially platinum-sensitive, progressive ovarian cancer. “Platinum-based chemotherapy should be used as a control arm in future trials of new drugs in this setting,” they wrote.—Zachary Bessette