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Women with ovarian cancer have few nonplatinum-based chemotherapy options. At the 33rd ESMO Congress in September 2008, researchers reported findings from OVA-301, a phase III trial that compared efficacy and safety of trabectedin (Yondelis) in combination with pegylated liposomal doxorubicin (PLD) versus PLD monotherapy in women with relapsed ovarian cancer. Trabectedin is a novel anti-tumor agent derived from sea squirts approved in the treatment of soft tissue sarcomas and ovarian cancer.
Bradley J. Monk, MD, associate professor of obstetrics and gynecology at the University of California in Irvine, conducted the trial in collaboration with an international group of researchers from 21 countries. Researchers randomized 672 women (median age, 57 y) whose ovarian cancer had relapsed following first-line chemotherapy to PLD 30 mg/m² over 60 to 90 minutes followed by trabectedin 1.1 mg/m² over 3 hours every 3 weeks or PLD 50 mg/m² every 4 weeks.
All the women were performance status 2 or less and had previously undergone 6 full cycles of platinum-based chemotherapy, and all experienced cancer progression; one-third relapsed <6 months after the last dose of first-line therapy, and two-thirds experienced cancer relapse ≥6 months after therapy. Researchers noted that trabectedin appeared ineffective in those women whose cancer was most resistant to first-line chemotherapy, as indicated by recurrence in <6 months or persistence through therapy.
Overall median PFS was 7.3 months for women treated with PLD plus trabectedin and 5.8 for the women treated with PLD alone (HR, 0.79; P
= .019). Women in both groups whose cancer relapsed ≥6 months after first-line treatment experienced slightly longer median PFS, at 9.2 months for the combined treatment group and 7.5 months for the PLD monotherapy cohort.
Women in the combination therapy group were significantly more likely to experience neutropenia and increased liver enzymes than those in the monotherapy group. Researchers noted that these adverse events were managed with dose adjustments, appropriate monitoring, and dose delays. Women in the combination therapy group were less likely to develop hand and foot syndrome.
As of the September meeting, overall survival had not yet been attained, although preliminary findings indicated that patients in the trabectedin arm had a 15% reduction in the risk of mortality (P
Monk BJ. A randomized phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD in relapsed, recurrent ovarian cancer. Paper presented at: 33rd annual meeting of the European Society for Medical Oncology; September 15, 2008; Stockholm, Sweden.