Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial

Background: With our growing insight into the molecular heterogeneity and biological characteristics of breast cancer, individualized treatment is the future of cancer treatment. In this prospective Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series study – neoadjuvant therapy (FASCINATE-N) trial, we classify breast cancer patients using multiomic characteristics into different subtypes to evaluate the efficacy of precision-based targeted therapies compared to standard neoadjuvant chemotherapy. Methods and design: The FASCINATE-N trial is a prospective, randomized, precision-based umbrella trial that plans to enroll 716 women with early breast cancer. After enrollment, patients will first be divided into three groups: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HER2+, and HR−/HER2−. The HR+/HER2− patients are further stratified using fusion and clustering of similarity network fusion (SNF) algorithm into four subtypes; HER2+ patients are divided into HR+/HER2+ and HR−/HER2+ subtypes; and HR−/HER2− patients are stratified using the Fudan University Shanghai Cancer Center classification. For the assignment of drugs to patients, Bayesian methods of adaptive randomization will be used. The primary endpoint is pathological complete response rate; secondary endpoints include 3-year invasive disease-free survival, overall response rate, and toxicities according to common terminology criteria for adverse events (CTCAE) scale version 4.0 and the ratio of patients with complete cell cycle arrest (Ki67 < 2.7%) in HR+/HER2+ breast cancer. Discussion: The goal of our trial is to test the efficacy of our subtyping-based treatment in a neoadjuvant setting and to conduct a pilot study into the efficacy of targeted therapies within each precision-based subtype. The precision-based treatment arm can be updated with the refinement of our subtyping method, the discovery of new targets, and the development of novel targeted drugs. Our trial offers a unique opportunity to provide patients with individualized neoadjuvant therapy and test promising novel treatments that may further benefit patients. Trial registration: ClinicalTrials.gov identifier: NCT05582499 ( https://classic.clinicaltrials.gov/ct2/show/NCT05582499 )

sj-docx-1-tam-10.1177_17588359231225032 – Supplemental material for Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial

Supplemental material, sj-docx-1-tam-10.1177_17588359231225032 for Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial by Wen-Jia Zuo, Li Chen, Yu Shen, Zhong-Hua Wang, Guang-Yu Liu, Ke-Da Yu, Gen-Hong Di, Jiong Wu, Jun-Jie Li and Zhi-Ming Shao in Therapeutic Advances in Medical Oncology</p

Anthracycline-free or short-term regimen as adjuvant chemotherapy for operable breast cancer: A phase III randomized non-inferiority trial

International audienc

Clinical characteristics and drug tolerance for infection in patients with agranulocytosis and fever in Shanghai

The characteristics of distribution of Pseudomonas aeruginosa in patients with agranulocytosis and fever in 12 hospitals in Shanghai from 2012 to 2014 were retrospectively analyzed. WHONET 5.6 software was used to analyze the results of drug sensitivity test. Data from different diseases, different sample sources, and drug sensitivity tests were statistically analyzed to investigate the clinical distribution characteristics and drug resistance of Pseudomonas aeruginosa in patients with agranulocytosis and fever in Shanghai, China. This study revealed that, among these 109 strains of P. aeruginosa , they were mainly found in patients with acute myelocytic leukemia (AML; 48 strains, 44.04%) and patients with acute lymphocytic leukemia (ALL; 36 strains, 33.03%). The specimen sources were mainly respiratory tract secretions (58 strains, 53.21%) and blood (21 strains, 19.26%). The P. aeruginosa isolates from neutropenic sepsis patients showed high sensitivity to the following antibiotics: piperacillin/tazobactam, cefepime, ciprofloxacin, ceftazidime, and amikacin with 91.1%, 89%, 89%, 87.9%, and 85.7% of isolates being sensitive, respectively. Furthermore, for P. aeruginosa isolates from the AML group of patients, the lowest antibiotic resistance rates were seen for ciprofloxacin (0%), cefoperazone/sulbactam (2.1%), and cefepime (7.1%), while for the ALL group the lowest antibiotic resistance rates were seen for piperacillin (2.8%), ceftazidime (2.8%), and cefepime (2.8%). Isolates from AML patients (21.3%) were significantly more likely to be piperacillin resistant than those from the ALL patients (2.8%). Therefore, P. aeruginosa infection is relatively common in patients with agranulocytosis and fever. The strains had a certain degree of resistance to commonly used antibiotics