Trabectedin, Bevacizumab, Platinum Chemotherapy Combo May Work, But Safety a Concern, Study Finds

Women with ovarian cancer who are partially sensitive to platinum-based chemotherapy may benefit from a new combination therapy — but safety concerns need to be addressed first, a study suggests.

The new study proposes a combination of trabectedin and bevacizumab with platinum-based chemotherapy for these patients, whose disease relapsed within six to 12 months after treatment.

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.