TY - JOUR
T1 - Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy
T2 - a phase Ib study
AU - Fan, Ying
AU - Zhang, Qingyuan
AU - Yan, Min
AU - Qu, Xiujuan
AU - Yin, Yongmei
AU - Sun, Tao
AU - Yang, Jin
AU - Wang, Ying
AU - Wang, Xu
AU - Niu, Zhaofeng
AU - Wang, Xinshuai
AU - Sun, Sanyuan
AU - Zhao, Weihong
AU - Liu, Yanping
AU - Niu, Miao
AU - Zhao, Xuemin
AU - Xu, Binghe
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2025/12
Y1 - 2025/12
N2 - This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m2). In part 2, patients were enrolled in two cohorts (mTNBC and HER2-negative breast cancer brain metastasis [BCBM]), and received HE072 70 mg/m2 every two weeks (Q2W). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and treatment emergent adverse events (TEAEs). The secondary endpoints were pharmacokinetic profiles and efficacy including objective response rate (ORR) and disease control rate (DCR) (all patients) and Central Nervous System ORR and clinical benefit rate (CBR, for patients with HER2-negative BCBM), duration of response, progression free survival (PFS), overall survival (OS). A total of 119 patients were enrolled, including 101 mTNBC and 18 HER2-negative BCBM. One dose limiting toxicity (grade 3 nausea and vomiting) occurred at 70 mg/m2, and the MTD was not reached. The most common ≥ grade 3 TEAEs related to HE072 included neutropenia (21.0%), leukopenia (18.5%), diarrhea (10.1%). Among 87 evaluable patients with mTNBC, 22 patients (25.3%) achieved overall response. The DCR was 67.8% (59/87). The median PFS and OS were 4.8 months and 14.1 months, respectively. The RP2D was 70 mg/m2 Q2W. Promising antitumor activity in heavily pre-treated patients with mTNBC was observed, which warrants further validation.
AB - This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m2). In part 2, patients were enrolled in two cohorts (mTNBC and HER2-negative breast cancer brain metastasis [BCBM]), and received HE072 70 mg/m2 every two weeks (Q2W). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and treatment emergent adverse events (TEAEs). The secondary endpoints were pharmacokinetic profiles and efficacy including objective response rate (ORR) and disease control rate (DCR) (all patients) and Central Nervous System ORR and clinical benefit rate (CBR, for patients with HER2-negative BCBM), duration of response, progression free survival (PFS), overall survival (OS). A total of 119 patients were enrolled, including 101 mTNBC and 18 HER2-negative BCBM. One dose limiting toxicity (grade 3 nausea and vomiting) occurred at 70 mg/m2, and the MTD was not reached. The most common ≥ grade 3 TEAEs related to HE072 included neutropenia (21.0%), leukopenia (18.5%), diarrhea (10.1%). Among 87 evaluable patients with mTNBC, 22 patients (25.3%) achieved overall response. The DCR was 67.8% (59/87). The median PFS and OS were 4.8 months and 14.1 months, respectively. The RP2D was 70 mg/m2 Q2W. Promising antitumor activity in heavily pre-treated patients with mTNBC was observed, which warrants further validation.
UR - https://www.scopus.com/pages/publications/85214008681
U2 - 10.1038/s41467-024-55090-4
DO - 10.1038/s41467-024-55090-4
M3 - 文章
C2 - 39746964
AN - SCOPUS:85214008681
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3
ER -
