Trabectedin shows promise in recurrent ovarian cancer

STOCKHOLM (Reuters Health) - The investigational agent trabectedin plus pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) in ovarian cancer patients who have relapsed after receiving standard first-line chemotherapy, according to phase III data reported at the 33rd Congress of the European Society for Medical Oncology (ESMO).

Trabectedin, which is a synthetic version of a compound first isolated from the sea squirt Ecteinascidia turbinata, is approved in Europe for the treatment of patients with advanced soft tissue sarcoma.

"Importantly, the findings challenge the current treatment paradigm for platinum-sensitive women whose ovarian cancer recurs six months or later after their initial treatment, which involves re-treatment with a platinum compound with either carboplatin/paclitaxel or carboplatin/gemcitabine," Dr. Bradley J. Monk said.

"Our data demonstrate a role for a non-platinum doublet in this population," said Dr. Monk, associate professor of obstetrics and gynecology at the University of California, Irvine.

Dr. Monk and colleagues randomized 672 women to PLD 30 mg/m² plus trabectedin 1.1 mg/m² every three weeks, or to PLD alone, 50 mg/m² every 4 weeks.

All subjects had progressed after six full cycles of chemotherapy and two-thirds had relapsed 6 months or longer after the last dose of first-line therapy.

Results showed a median progression-free survival of 7.3 months with PLD plus trabectedin versus 5.8 months for PLD alone (hazard ratio = 0.79, p = 0.019).

In women who had relapsed more than 6 months after first-line therapy, the median PFS was 9.2 months for the group assigned to combination treatment compared to 7.5 months for the group receiving PLD as monotherapy.

Median overall survival has not yet been reached.

Neutropenia and increased liver enzymes were significantly more common in the group on combination therapy. However, these events were managed with appropriate monitoring, dose adjustments, and delays. Hand and foot syndrome was less common in the group receiving combination therapy.

Dr. Monk said he was encouraged by the findings and countered the argument that an increase in progression-free survival of about a month and a half is minimal. "In the world of ovarian cancer, this difference is huge," he said.

Furthermore, he added, "Ovarian cancer patients need additional options, and a treatment that reduces the patient's risk of progression by 21% at any given time is very attractive to patients."

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