Titled “Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer,” the study was published in the British Journal of Cancer.
Trabectedin, marketed as Yondelis for the treatment of fat and smooth muscle tissue cancers, is a cancer-killing compound that works both by inhibiting the division of cancer cells and by modifying the cellular environment inside tumors. Bevacizumab — trade names Avastin and Mvasi — is another cancer treatment that works by inhibiting the tumor’s blood supply.
Preclinical data have suggested that these treatments could synergize with each other and with platinum-based therapy, but these combinations have not undergone rigorous clinical evaluation.
The new study details the results of a Phase 2 clinical trial (NCT01735071) that tested this combination, with or without platinum-based chemotherapy, in people with partially platinum-sensitive ovarian cancer.
“The partially platinum-sensitive population enabled us to explore though not formally comparing the efficacy and safety profile of two new chemotherapic regimens: a platinum-free regimen with trabectedin and bevacizumab [BT arm] and a platinum-based triplet with carboplatin, trabectedin and bevacizumab [BT+C arm],” the researchers said.
Carboplatin, usually given into a vein, is a chemotherapy drug used to treat ovarian and lung cancer.
The trial enrolled 71 women, with an average age of ~61 years, whose ovarian cancer had recurred between six to 12 months after their most recent platinum-based chemotherapy regimen. It was the first or second such regimen for all participants.
Primary endpoints were the time patients lived without disease worsening — a measure called progression-free survival — and incidence of severe toxicity at six months of treatment with BT or BT+C.
In the BT arm of the study, 44 participants were enrolled and analyzed at six months. Of these, 75% remained alive and without disease progression at six months, and 16% experienced severe toxicities. The median progression-free survival was 9.1 months and patients lived for a median of 23.2 months.
The BT+C arm included 20 women, three of whom progressed — amounting to a six-month progression-free survival of 85%. These participants had a median progression-free survival of 21.1 months and an overall survival of 42.6 months.
However, toxicities in this group were high: 45% of the women experienced severe toxicities, and 40% received fewer than the recommended number of cycles of carboplatin due to adverse events.
“The BT regimen showed worth-while clinical activity and limited toxicity that can position it as a therapeutic opportunity for women with partially platinum-sensitive disease,” the researchers concluded, adding that “the apparent good activity of the BT+C regimen warrants further studies with a re-modulated schedule to limit its toxicity.”
“The possible synergy between trabectedin, bevacizumab and carboplatin could translate into clinical reality wherever other platinum combinations fail,” the researchers added.