Patient-derived tumor cell clusters (PTC) guiding-neoadjuvant therapy of HER2-positive breast cancer: A prospective randomized phase II clinical trial.

581 Background: In a previous study, the patient-derived tumor-like cell clusters (PTC) were confirmed to be an accurate medicine effect-predicting model in vitro for clinical practice (1). We designed this prospective randomized phase II trial to research if this PTC-guiding strategy could improve the effect of neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2) positive breast cancer (NCT05103293). Methods: We enrolled HER2-positive early breast cancer patients planning for neoadjuvant therapy to accept the PTC-guiding regimen as an experimental group or regimens of the physician's choice as a control group randomly. All eligible patients in the experimental group would receive medicine-sensitive testing by PTC then accepted the regimen with the highest PTC killing rate (30% as the lowest cut-off value) from the three candidate regimens (Cyclophosphamide combined with epirubicin -- Docetaxel combined with trastuzumab and pertuzumab, EC-THP, Docetaxel and carboplatin with trastuzumab and pertuzumab, TCbHP and Docetaxel with trastuzumab and pyrotinib, THPy). The primary endpoint is pathological complete response (pCR) in two groups using superiority odd ratio Fisher's exact test (one-sided alpha =0.05, power of 80%, and superiority margin at 0.1). The secondary endpoints are Miller-Payne (MP) grade 4~5 proportion, objective response rate (ORR), disease-free survival (DFS), and overall survival (OS). Results: Finally, 86 patients were enrolled in this study, 44 in the experimental and 42 in the control groups. The experimental group had 65.9% of pCR, significantly higher than 42.9% in the control group (Hazard ratio=0.388, P=0.033). The PTC-guiding treatment also considerably increased MP 4~5 proportion (79.5% vs. 59.4%, Hazard ratio=0.283, P=0.009) and objective response rate (90.9% vs 71.4%, Hazard ratio=0.250, P=0.027). After a two-year medium follow-up, the disease-free survival of the PTC-guiding treatment group was 84.1% higher than 71.4% of the control group without a significant difference (Log Rank, P=0.106). The two groups had similar overall survival (Log Rank, P=0.958). Furthermore, the PTC-guiding strategy significantly impacted pCR in univariate and multivariate regression analyses but not survival. Conclusions: In this trial, we concluded that the PTC-guiding neoadjuvant therapy could improve the effect, including pCR, MP score, and ORR in HER2-positive breast cancer. 1. Yin et al., Sci.Transl. 2020. Clinical trial information: NCT05103293 .