The combination of the investigational agent trabectedin with pegylated liposomal doxorubicin (PLD) resulted in a 1.5-month improvement in progression-free survival in women with recurrent ovarian cancer. Final information about overall survival is not yet available. These findings were recently published in the Journal of Clinical Oncology.
Ovarian cancer is diagnosed in roughly 22,000 women each year in the United States, where it remains the leading cause of death from gynecologic cancers. Although most ovarian cancer patients initially respond to platinum-based chemotherapy, many will eventually experience a return (relapse) of their cancer. Ovarian cancer patients who experience a relapse after treatment with platinum-based chemotherapy are characterized as either platinum-sensitive (relapse/progression occurs more than six months after last treatment); platinum-resistant (relapse/progression occurs less than six months after last treatment); or platinum refractory (relapse/progression while undergoing treatment). Outcomes remain poor after treatment of relapsed disease, and researchers continue to explore new approaches to treatment.
Trabectedin is an investigational agent that is derived from marine compounds. Trabectedin binds to an area of the DNA called the minor groove. This binding inhibits cellular replication and causes the cell to destroy itself.
In this randomized Phase III study, researchers evaluated the safety and efficacy of trabectedin plus PLD versus PLD alone in 672 ovarian cancer patients with recurrent disease who had been previously treated with platinum-based chemotherapy. Patients were randomized to receive either trabectedin plus PLD (30 mg/m2) every three weeks or PLD (50 mg/m2) alone every four weeks.
Patients in the combination arm experienced a progression-free survival of 7.3 months versus 5.8 months in the PLD-alone arm. In the subset of patients with platinum-sensitive disease, progression-free survival was 9.2 months with trabectedin plus PLD versus 7.5 months with PLD alone. Patients with platinum-resistant disease did not appear to experience an improvement in progression-free survival with the addition of trabectedin.
Patients in the combination arm experienced more neutropenia (42% versus 17%), hyperbilirubinemia (15% versus 5%), and nonfatal congestive heart failure-related diagnoses (six patients versus one patient) than patients in the PLD-alone arm. Although patients in the single-agent arm experienced hand-foot syndrome more frequently, this may be due to the higher dose of PLD in the single-agent arm.
The researchers concluded that the combination of trabectedin and PLD improved progression-free survival compared with PLD alone in patients with recurrent ovarian cancer. The benefit appeared to be limited to patients with platinum-sensitive disease. Although trabectedin plus PLD may provide an additional treatment option for these patients, the researchers point out that “re-treatment with platinum-based therapy remains a viable option in this setting.”