Abstract PO1-06-01: Clinical Efficacy of Tumor Organoid-Guided Cancer Therapy for Locally Advanced Unresectable or Metastatic Breast Cancer

Abstract Purpose: Patient-derived organoids (PDOs) may facilitate treatment selection, but the feasibility of using breast cancer PDOs to guide personalized treatment in clinical practice has not been fully investigated. This study aimed to assess the clinical efficacy of treatment guided by PDO drug sensitivity tests (OGT) versus treatment of physician’s choice (TPC) in patients with locally advanced unresectable or metastatic breast cancer (MBC) and to explore the potential of PDOs to reveal mechanisms underlying treatment resistance. Methods: Patients diagnosed with MBC were recruited between January 2020 and August 2022. PDOs were established from biopsies specimens or malignant effusion samples. The efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving OGT were matched 1:2 by nearest neighbor propensity scores with patients receiving TPC. The primary clinical outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Results: 46 PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 81.1% (95% CI 67.6%-91.9%) in predicting patients' clinical responses. 36 OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs 5.0 months; unadjusted hazard ratio 0.53 95% CI 0.33-0.85; P=0.01) and improved disease control (88.9% vs 63.8%; unadjusted odd ratio 4.26 1.44-18.62) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis uncovered differentially modulated pathways implicated in DNA repair and transcriptional regulation in patients less sensitive to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in patients less sensitive to palbociclib. Conclusions: MBC patients treated with OGT were associated with superior progression-free survival and disease control compared with TPC. PDO-based functional precision medicine is a feasible strategy for treatment optimization and customization in MBC and may enhance our understanding of therapeutic resistance. Citation Format: Ying-Yi Lin, Hong-Fei Gao, Hong Li, Bo-Lei Du, Min-Yi Cheng, Jia-Chen Zou, Xing-xing Zheng, Teng Zhu, Ting-Ting Li, Sheng Li, Kun Wang. Clinical Efficacy of Tumor Organoid-Guided Cancer Therapy for Locally Advanced Unresectable or Metastatic Breast Cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-01.