Tibremciclib or Placebo Plus Fulvestrant in Hormone Receptor–Positive and ERBB2 -Negative Advanced Breast Cancer After Endocrine Therapy

作者：Zhonghua Tao, Jian Zhang, Qiufan Zheng, Yongsheng Wang, Li Cai, Hongyan Xu, Xinhua Xu, Xiangshun Kong, Sijuan Ding, Chunfang Hao, Hao Wang, Hong Zong, Xin Jin, Xinshuai Wang, Li Yang, Xiuli Yang, Ian Li, Xiaoya Du, Hui Chen, Pengxiang Wu, Peiqi Li, Li Mao, Lieming Ding, Xichun Hu, Shusen Wang · 发表于：JAMA Oncology · 年份：2025 · DOI：10.1001/jamaoncol.2025.2092 · 被引用次数：3 · 研究领域：Advanced Breast Cancer Therapies、Cancer-related Molecular Pathways、Breast Cancer Treatment Studies

Importance: Cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapy (ET) are now considered the standard treatment regimen for hormone receptor-positive (HR+) and ERBB2 (formerly HER2)-negative (ERBB2-) advanced breast cancer (ABC). Tibremciclib (BPI-16350), a novel CDK4/6 inhibitor, has demonstrated favorable tolerability and promising antitumor activity as a monotherapy or combined with fulvestrant among patients with HR+/ERBB2- ABC in a phase 1 trial. Further investigations are necessary to assess the efficacy and safety of tibremciclib. Objective: To compare tibremciclib plus fulvestrant and placebo plus fulvestrant in terms of efficacy and safety among patients with HR+/ERBB2- ABC who exhibited disease progression after ET. Design, Setting, and Participants: The TIFFANY trial was a double-blind, placebo-controlled, phase 3 randomized clinical trial of patients with HR+/ERBB2- ABC who had experienced progression while receiving prior ET and had received no more than 1 line of chemotherapy. This trial was conducted at 69 Chinese centers between May 25, 2022, and April 25, 2023. The data cutoff date for this analysis was March 31, 2024. Interventions: Patients were randomly assigned to receive tibremciclib (400 mg, orally, once daily) plus fulvestrant or placebo plus fulvestrant at a 2:1 ratio until disease progression, death, or treatment discontinuation for various reasons. Main Outcomes and Measures: The primary end point was investigator-assessed pr...