Phase IB and II study of ribociclib with trastuzumab plus endocrine therapy in HR+/HER2+ advanced breast cancer patients: Korean Cancer Study Group BR 18-2 MINI trial.

作者：Joohyuk Sohn, Seung‐Taek Lim, Jae Ho Jeong, Kyung-Hun Lee, Keun Seok Lee, Yong Wha Moon, Ji‐Yeon Kim, Jieun Lee, Hee Jun Kim, Yee Soo Chae, Jee Hung Kim, Suee Lee, In Hae Park, Seok Yun Kang, Kyong Hwa Park, Eun Kyung Cho, Han Jo Kim, Gun Min Kim, Min Hwan Kim, Kyoo Hyun Kim · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.1016 · 被引用次数：2 · 研究领域：Advanced Breast Cancer Therapies、HER2/EGFR in Cancer Research、Lung Cancer Research Studies

1016 Background: In HER2+ advanced breast cancer (ABC), standard treatment has been anti-HER2 therapy with chemotherapy, regardless of hormone receptor status. While prior studies support the use of CDK4/6 inhibitors with anti-HER2 and endocrine therapy in pretreated HR+/HER2+ ABC, data on their first line use without chemotherapy are limited. This study investigates ribociclib, trastuzumab, and letrozole as a first-line combination in HR+/HER2+ ABC. Methods: This multicenter, single-arm, prospective trial was conducted across 17 academic institutions in South Korea (NCT03913234). Eligible patients were HR+/HER2+ ABC with no prior systemic therapy for metastatic disease. The Phase IB study used a 3+3 design to determine the recommended Phase II dose (RPIID) of ribociclib with fixed doses of letrozole (2.5 mg QD) and trastuzumab (8 mg/kg loading, then 6 mg/kg every 3 weeks). The Phase II trial evaluated efficacy and safety at the RPIID. The primary endpoint was progression-free survival (PFS), targeting an improvement from 8 to 12 months. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety. PAM50 testing assessed correlations between intrinsic subtype and treatment efficacy. Results: Phase IB (n = 13) identified the RPIID as ribociclib 600 mg QD, with one dose-limiting toxicity (Grade 3 ALT elevation) at 400 mg. In Phase II, 77 patients were enrolled, with a median age of 61 years (range 31–85), 18.2% (14/77...