– The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.

After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.

Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.

“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).

The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.

Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.

Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.

Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.

A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.