Interim analysis of a phase I/IIa trial assessing E39+GM-CSF, a folate binding protein vaccine, to prevent recurrence in ovarian and endometrial cancer patients.

BACKGROUND: Folate binding protein(FBP) is an immunogenic protein over-expressed in endometrial(EC) and ovarian cancer(OC). We are conducting a phase I/IIa trial of E39 (GALE 301)+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent recurrences in disease-free EC and OC patients. This interim analysis summarizes toxicity, immunologic responses, and clinical outcomes to date. METHODS: HLA-A2+ patients were vaccinated(VG), and HLA-A2- or -A2+ patients were followed as controls(CG). Six monthly intradermal inoculations of E39+250mcg GM-CSF were administered to VG. Demographic, safety, immunologic, and recurrence rate(RR) data were collected and evaluated. RESULTS: This trial enrolled 51 patients; 29 in the VG and 22 in the CG. Fifteen patients received 1000mcg E39, and 14 received <1000mcg. There were no clinicopathologic differences between groups(all p ≥ 0.1). E39 was well-tolerated regardless of dose. DTH increased pre- to post-vaccination (5.7±1.5 mm vs 10.3±3.0 mm, p = 0.06) in the VG, and increased more in the 1000mcg group (3.8±2.0 mm vs 9.5±3.5 mm, p = 0.03). With 12 months median follow-up, the RR was 41% (VG) vs 55% (CG), p = 0.41. Among the 1000mcg patients, the RR was 13.3% vs 55% CG, p = 0.01. Estimated 2-year DFS was 85.7% in the 1000mcg group vs 33.6% in the CG (p = 0.021). CONCLUSIONS: This phase I/IIa trial reveals that E39+GM-CSF is well-tolerated and elicits a strong, dose-dependent in vivo immune response. Early efficacy results are promising in the 1000 mcg dose cohort. This study proves the safety and establishes the dose of E39 for a larger prospective, randomized, controlled trial in HLA-A2+ EC and OC patients to prevent recurrence.

Analysis of Clinical and Pathologic Factors of Pure, Flat Epithelial Atypia on Core Needle Biopsy to Aid in the Decision of Excision or Observation.

BACKGROUND: The optimal treatment of flat epithelial atypia (FEA) found on breast core needle biopsy (CNB) is controversial. We performed a retrospective review of our institutional experience with FEA to determine if excisional biopsy may be deferred. METHODS: Surgical records from 2009 to 2012 were reviewed for FEA diagnosis. After exclusion for concomitant lesions, CNBs of pure FEA were classified using a previously agreed upon descriptor of "focal" versus "prominent". Data was analyzed with the Fisher's Exact and Student-t test as appropriate. RESULTS: Of 71 CNBs evaluated, pure FEA was identified on 27 CNBs. Final excisional biopsy was benign in 24 of 27 cases (88%) with associated ductal carcinoma in-situ (DCIS) in 3 of 27 cases (11%). Eighteen of 27 (67%) CNBs were classified as focal while 9 (33%) were described as prominent. Zero of the 18 focal patients had a malignancy compared to 3 of the 9 in the prominent group (0% vs 33%, p=0.02). Of the 27 pure FEA CNBs, 6 patients had a personal history of breast carcinoma, five DCIS and one invasive ductal carcinoma. No malignancies were found in the 21 patients without a personal history of breast carcinoma versus three in the patients with a positive history (0/21 v 3/6, p=0.007). CONCLUSIONS: Our data suggests those women who have adequate sampling and sectioning of CNBs, with focal, pure FEA on pathology, and are without a personal history of breast cancer may undergo a period of imaging surveillance. Conversely, patients with a history of breast cancer or pure, prominent FEA on CNB disease should proceed to excisional biopsy.