A prospective phase II study of neoadjuvant therapy guided by personalized drug-testing on patient-derived tumor-like cell clusters for early breast cancer.
Authors: Wang Chaobin , Zhang Xiangui , Yin Shenyi , Liu Miao , Yang Houpu , Xie Fei , Peng Yuan , Yang Yang , Wang Siyuan , Du Wei , Xi Jianzhong , Wang Shu 
Published: July 2024

e12625 Background: Individual tumors of breast cancer patients possess unique characteristics that may influence their neoadjuvant therapy (NAT) response to specific cytotoxic agents and treatment choices. Therefore, it is essential to have a platform that can assist in the personalized selection of chemotherapy for individual patients. Previously, we reported an in vitro model called patient-derived tumor-like cell clusters (PTC), which can structurally and functionally recapitulate original tumors. Retrospective research has shown that PTC hold potential as reliable pre-clinical drug testing model for guiding NAT therapeutic options in early breast cancer patients. Methods: This prospective, phase II, open-label study aimed to validate the efficacy of drug screening on patient-derived tumor-like cell clusters (PTCs). TNBC and HER2 positive patients received neoadjuvant therapy based on subtype and personalized drug testing on PTCs. TNBC patients were treated based on drug testing, receiving either TA (taxanes combined with anthracyclines) or TP (taxanes combined with carboplatin). HER2 positive patients received treatment based on drug testing, including THP (taxanes, trastuzumab and pertuzumab) or TCbHP (taxanes, carboplatin, trastuzumab, and pertuzumab). Sample size calculation was performed using Fleming's two-stage design. For TNBC patients, if 10 or more out of 20 patients achieved pCR in the first stage, an additional 26 patients would be enrolled in the second stage. For HER2-positive patients, the sample size was same with TNBC patients. The study was approved by the Ethics Committee of Peking University People's Hospital in Beijing and was registered on ClinicalTrials.gov (NCT04750122, NCT04836156). This time, we report the results of the first stage. Results: Among 20 enrolled TNBC patients in the first stage, 15 achieved pCR with the rate of 75%. 17 patients (85%) had RCB 0-I score while 3 patients (15%) had an RCB-II score. 14 patients received TP as it demonstrated greater sensitivity in vitro. Out of these 14 patients, 10 patients (71.4%) achieved pCR. Six patients received TA as it was more effective in drug testing. Among these patients, 5 (83.3%) patients achieved pCR. Out of 20 enrolled HER2-positive patients, 16 achieved pCR, resulting in a pCR rate of 80%. Six patients received THP treatment based on their sensitivity to this regimen in drug testing. Among these patients, 5 (83.3%) achieved a pCR. 14 patients who were sensitive to TCbHP but not to THP in drug testing received TCbHP treatment. Among these patients, 11 (78.6%) achieved pCR. The non-pCR patients had 2 RCB-II score and the ORR was 100% for all 14 patients. Conclusions: Our results demonstrate that personalized drug testing on PTCs can effectively guide the choice of neoadjuvant therapy for early TNBC and HER2-positive breast cancer patients. Clinical trial information: NCT04750122 , NCT04836156 .