Addition of Vintafolide to Pegylated Liposomal Doxorubicin Improves Progression-Free Survival in Platinum-Resistant Ovarian Cancer
In a randomized phase II trial reported in the Journal of Clinical Oncology by R. Wendel Naumann, MD, of Carolinas Medical Center in Charlotte, North Carolina, and colleagues, the addition of vintafolide to pegylated liposomal doxorubicin improved progression-free survival in women with recurrent platinum-resistant ovarian cancer. Vintafolide (EC145) is a folic acid–desacetylvinblastine conjugate that binds to folate receptors expressed on the majority of epithelial ovarian cancers. The progression-free survival benefit was most marked in patients with 100% of lesions positive for folate receptors as identified by the folate receptor–targeted imaging agent 99mTc-etarfolatide.
Study Details
In the open-label international study, 149 women with recurrent platinum-resistant ovarian cancer who had received two or fewer prior cytotoxic regimens were randomly assigned 2:1 to intravenous pegylated liposomal doxorubicin at 50 mg/m2 once every 28 days with (n = 100) or without (n = 49) intravenous vintafolide at 2.5 mg three times per week during weeks 1 and 3. Etarfolatide scanning was optional. The primary endpoint was progression-free survival.
Baseline disease characteristics were generally similar in the vintafolide and liposomal doxorubicin–alone groups. More patients in the vintafolide group had no residual disease (44% vs 33%) after primary debulking, with more liposomal doxorubicin patients having ≤ 1 cm (21% vs 39%). The sum of target tumor lesions was almost twice as great in the vintafolide group (120 vs 74 mm) and baseline CA-125 level (< 200 U/mL in 59% vs 65%) and platinum-free interval (> 3–6 months in 56% vs 75.5%) favored better prognosis in the liposomal doxorubicin–alone group.
Prolonged Progression-Free Survival
Median progression-free survival was 5.0 months in the vintafolide group vs 2.7 months in the liposomal doxorubicin–alone group (hazard ratio [HR] = 0.63, P = .031). Results were similar on analysis stratified by platinum failure and CA-125 level (HR = 0.605, P = .026) and on analysis adjusting for age, time from platinum failure, CA-125 level, geographic region, tumor size, months since last platinum treatment, and Eastern Cooperative Oncology Group performance status (HR = 0.60, P = .034).
Best Subgroup Outcome
A total of 61 patients in the vintafolide group (61%) and 33 in the liposomal doxorubicin–alone group (67%) had etarfolatide scans, with 23 and 15 having 100% folate receptor–positive lesions, 25 and 11 having 10% to 90% positive lesions, and 13 and 7 having 0% positive lesions. The greatest progression-free survival benefit was observed in patients with 100% of lesions positive (median, 5.5 vs 1.5 months, HR = 0.38, P = .013), whereas there were no significant differences between patients with 10% to 90% positive lesions (median, 5.7 vs 7.0 months, HR = 0.87, P = .79) or those with 0% positive lesions (median, 3.8 vs 5.4 months, HR = 1.81, P = .468).
Toxicities
Adverse events of any grade that were significantly more common in the vintafolide group were neutropenia (44% vs 24%), abdominal pain (36% vs 18%), peripheral sensory neuropathy (29% vs 12%), and leukopenia (23% vs 8%; all P < .05). Grade 3 or 4 adverse events were significantly more common in the vintafolide group (76% vs 54%, P = .009), including neutropenia (23% vs 10%, P = .52), palmar-plantar erythrodysesthesia syndrome (11% vs 2%, P = .063), and leukopenia (9% vs 0%, P = .031); grade 3 or 4 nausea was more common in the liposomal doxorubicin–alone group (1% vs 8%, P = .036).
The investigators concluded, “Vintafolide plus [pegylated liposomal doxorubicin] is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.”
The study was supported by Endocyte, and medical writing and editorial assistance was provided by TRM Oncology and supported by Endocyte.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
