Extending Platinum-Free Interval Might Reduce Survival in Recurrent Ovarian Cancer

Contrary to expectations, extending platinum-free interval (PFI) with pegylated liposomal doxorubicin (PLD), topotecan, or gemcitabine does not improve-and might diminish-overall survival (OS) among patients with recurrent ovarian cancer, according to a randomized phase III trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 5505).

“Prolongation of the platinum-free interval with a single-agent non-platinum therapy does not improve and even worsens the outcome of ovarian cancer patients recurring 6–12 months after a platinum-containing chemotherapy,” said lead study author Sandro Pignata, MD, of the National Institute for the Study and Treatment of Cancer in Napoli, Italy. “Immediate re-treatment with platinum-based chemotherapy remains the standard treatment strategy.”

Extending PFI with non-platinum therapy has long been hypothesized to improve patient outcomes.

MITO-8 is an open-label, randomized, phase III study of the association of survival outcome with single-agent non-platinum treatment to prolong PFI among patients with recurrent, partially platinum-sensitive ovarian cancer.

A total of 215 patients were enrolled in Italy, Belgium, and Germany between 2009 and 2015. Inclusion criteria for participants included ovarian cancer recurrence 6 to 12 months after platinum therapy; two or fewer previous chemotherapy lines; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; and normal bone marrow, heart, liver, and kidney function.

Patients were randomly assigned 1:1 to undergo treatment with either a platinum-based chemotherapy (n = 108; carboplatin + paclitaxel or carboplatin + gemcitabine for patients exhibiting neurotoxicity at baseline) or a non–platinum-based chemotherapy (n = 107; PLD or other approved single agents).

Non-platinum therapy prolonged PFI. However, it did not improve OS-and indeed, there was a trend toward worse OS (non-platinum vs platinum: 21.8 months vs 24.5 months; adjusted hazard ratio [HR], 1.38 [95% CI, 0.99–1.94]; P = .06). Median progression-free survival after second treatment was 12.8 months for patients treated with non–platinum-based chemotherapy vs 16.4 months for patients treated with platinum chemotherapy (HR, 1.41 [95% CI, 1.04–1.91]; P = .025).