Local Transdermal Delivery of Telapristone Acetate Through Breast Skin, Compared With Oral Treatment: A Randomized Double-Blind, Placebo-Controlled Phase II Trial

Oral breast cancer prevention medications entail systemic exposure, limiting acceptance by high-risk women. Delivery through the breast skin, although an attractive alternative, requires demonstration of drug distribution throughout the breast. We conducted a randomized double-blind, placebo-controlled phase II clinical trial comparing telapristone acetate, a progesterone receptor antagonist, administered orally (12 mg/day) or transdermally (12 mg/breast) for 4 ± 1 weeks to women planning mastectomy. Plasma and tissue concentrations, measured at five locations in the mastectomy specimen using liquid chromatography tandem mass spectrometry were compared. In 60 evaluable subjects, median drug concentration (ng/g tissue) was 103 (interquartile range (IQR): 46.3–336) in the oral vs. 2.82 (IQR: 1.4–5.5) in the transdermal group. Despite poor dermal permeation, within-breast drug distribution pattern was identical in both groups (R2 = 0.88, P = 0.006), demonstrating that transdermally and orally delivered drug is distributed similarly through the breast, and is strongly influenced by tissue adiposity (P < 0.0001). Other skin-penetrant drugs should be tested for breast cancer prevention

A brief report of toxicity end points of HER2 vaccines for the treatment of patients with HER2+ breast cancer

Ricardo Costa,1 Saif Zaman,2 Susan Sharpe,3 Irene Helenowski,4 Colleen Shaw,1 Hyo Han,1 Hatem Soliman,1 Brian Czerniecki1 1Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Morsani College of Medicine, University of South Florida, Tampa, FL, USA; 3Moffitt Biomedical Library, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 4Department of Preventive Medicine, Northwestern University, Chicago, IL, USA Abstract: Human epidermal growth factor receptor 2 (HER2)-targeted vaccines are under development, but have so far demonstrated only modest clinical efficacy. Additionally, there has been a lack of adequate safety assessment in large-scale prospective clinical trials. Therefore, we performed a meta-analysis of available clinical trial data to summarize the toxicity profiles of these treatments. Literature search was conducted in February 2018. The trials analyzed had at least one study arm consisting of HER2 vaccine monotherapy. Heterogeneity across studies was analyzed using I2 statistics. Data were analyzed using random-effects meta-analysis for absolute risk (AR). Eight trials and 248 patients were included. There was no evidence of heterogeneity between studies for grades 3/4 adverse events (AEs) or for death. The AR for treatment-related serious AEs was 5% with no treatment-related deaths. The AR of all-grade fatigue, injection site reaction, and fever/chills/rigors was 33%, 23%, and 31%, respectively. Asymptomatic drop in left ventricle ejection fraction was rare (8%). HER2 vaccines are well tolerated with increased AR of fatigue, injection site reactions, and fever/chills/rigors. Keywords: HER2, vaccines, immunity, dendritic cells, toxicit