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Vintafolide plus pegylated liposomal doxorubicin improved outcomes in ovarian cancer
The addition of vintafolide to pegylated liposomal doxorubicin extended PFS in patients with recurrent platinum-resistant ovarian cancer, according to study results.
Use of etarfolatide — a folate receptor-targeted imaging agent — also may help identify patients with ovarian cancer most likely to benefit from the combination, researchers wrote.
The analysis included 149 women who had undergone no more than two prior cytotoxic regimens.
Of them, 100 were randomly assigned to receive 2.5 mg IV vintafolide three times a week in 28-day cycles plus 50 mg/m2 IV pegylated liposomal doxorubicin on the first day of each cycle. The other 49 patients received pegylated liposomal doxorubicin alone.
PFS served as the primary endpoint.
Researchers reported significantly longer median PFS in the vintafolide arm (5 months vs. 2.7 months; HR=.63; 95% CI, 0.41-0.96).
Researchers calculated an 18% (95% CI, 11-27) objective response rate with vintafolide and a 12% (95% CI, 5-25) objective response rate with pegylated liposomal doxorubicin alone. The difference was not statistically significant.
Researchers also reported a significantly higher disease control rate — the combination of complete responses, partial responses and stable disease — in the vintafolide arm (73% vs. 53%).
Results showed no difference in OS between treatment arms, but researchers noted the study was not powered to test this endpoint.
The most common treatment-emergent adverse effects in patients assigned to vintafolide were fatigue, anemia, stomatitis and neutropenia. Significantly more patients treated with vintafolide reported leukopenia (P=.026), neutropenia (P=.021), abdominal pain (P=.026) and peripheral sensory neuropathy (P=.026).
Etarfolatide scan results indicated that patients with 100% folate receptor positivity benefited most from treatment.
“Vintafolide combined with pegylated liposomal doxorubicin has demonstrated improved clinical activity in terms of PFS compared with pegylated liposomal doxorubicin alone in patients with platinum-resistant ovarian cancer, and [the combination] is well tolerated,” researchers concluded. “The companion imaging diagnostic etarfolatide has identified a cohort likely to respond to the combination. These results provide strong rationale for the ongoing phase 3 investigation.”
Disclosure: The researchers report employment, leadership, consultant or advisory roles with, stock ownership in, and honoraria or research funding from Endocyte.
Perspective
Back to TopThis is an interesting report that provides strong support for exploring the use vintafolide in a phase 3 randomized trial (currently ongoing). Two additional comments are worthy of mention. First, the delivery of pegylated liposomal doxorubicin at a starting dose of 50 mg/m2 is problematic because it is well recognized that a lower dose is currently used outside the study setting. In the current trial, more than 40% of patients experienced stomatitis or hand-foot syndrome. One wonders if patients were informed they would have received a lower dose of this “standard-of-care” drug if they were not treated on this trial. Second, the conclusion of the paper states this “is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer.” This statement is inaccurate, as a phase 3 randomized trial has now revealed the superiority of chemotherapy plus bevacizumab (Avastin, Genentech) compared with bevacizumab alone in this clinical setting.