332P - Efficacy, safety and exploratory analysis of neoadjuvant tislelizumab plus nab-paclitaxel followed by epirubicin/cyclophosphamide for TNBC: A phase II TREND trial

Background

The optimal chemotherapy backbone and specific population of triple-negative breast cancer (TNBC) patients that benefit from neoadjuvant immunotherapy are not well established. This prospective, single-arm, phase II TREND trial assessed the efficacy and safety of tislelizumab plus nab-paclitaxel and anthracycline-based chemotherapy as a neoadjuvant treatment for TNBC.

Methods

Patients received tislelizumab every three weeks for eight cycles plus nab-paclitaxel weekly for four cycles, followed by four cycles of epirubicin-cyclophosphamide every three weeks prior to surgery. The primary endpoint was pathological complete response (pCR), with the secondary endpoints including overall response rate (ORR) and safety assessment. ScRNA-seq, bulk RNA-seq, TCR-seq, cyTOF and WES were performed on pre-treatment and post-treatment samples.

Results

Among 53 total enrolled patients, 44 completed the combined neoadjuvant therapy, 36 of whom were evaluable for pathological response. The primary end point was met, with 30 of 44 patients (68.18%) achieving pCR. Additionally, 14 out of 44 patients had a complete response (31.82%) and 27 (61.36%) showed partial response. The most commonly observed treatment-related adverse events (TRAEs) were hepatotoxicity and nausea, with 6 cases classified as grade 3 or higher adverse events. Immune response-related pathways, including TNF signaling pathway and T cell receptor signaling pathway, were enriched in pCR group. PROM1, GXYLT2 and FOXC1 were identified and construct pre-treatment model to predict response to immunotherapy. CDKN1A+ CD8 T lymphocytes are enriched in pCR group after neoadjuvant immunotherapy. Dynamic change of immune-related pathways at an early stage during the neoadjuvant immunotherapy may be associated with the treatment efficacy.

Conclusions

Among TNBC patients, neoadjuvant treatment of tislelizumab with platinum-free and low-dose chemotherapy showed promising clinical activity and was well-tolerated, without high incidence of TRAEs. Immune response were activated early in pCR patients, and enriched CDKN1A+ CD8 T lymphocytes after the NAT may be associated with the benefit from treatment.

Clinical trial identification

ChiCTR2000035262 Release date: August 7th, 2020.

Editorial acknowledgement

Legal entity responsible for the study

Department of Breast Surgery, Liaoning Cancer Hospital and Institute.

Funding

The National Natural Science Foundation of China (82203786, 82373231), the Natural Science Foundation of Liaoning Province of China (2022-YGJC-68, 2023-BS-105), and Chinese Young Breast Experts Research Project (CYBER-2021-A02, CYBER-2022-001).

Disclosure

All authors have declared no conflicts of interest.