Phase II trial of anlotinib-chemotherapy combination in pretreated HER2-negative metastatic breast cancer: therapeutic efficacy and proteomic biomarker profiling

The management of HER2-negative metastatic breast cancer (MBC) in the second-line or later setting remains challenging, due to the absence of standardized regimens and the limited efficacy of chemotherapy. Here, we report a prospectively, single-arm, phase II study evaluating anlotinib plus chemotherapy in patients with HER2-negative MBC (n = 33) who had progressed after at least one prior line of systemic therapy for metastatic disease. The primary endpoints were median progression-free survival (mPFS) and overall survival (OS), while secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety. Exploratory proteomic profiling using the Olink Target 96 Immuno-Oncology panel was performed on baseline serum samples to identify potential predictors of response. After a median follow-up of 25.9 months and the median number of prior systemic therapy lines was 2 (range, 1-4). The mPFS was 8.3 (95% CI: 6.3-10.3) months, and the mOS was 22.2(95% CI: 13.1-31.3) months. The ORR was 33.3%, DCR reached 90.9% and CBR stood at 60.6%. Proteomic analysis indicated that higher baseline serum levels of proteins including CSF-1 were associated with shorter PFS (P < 0.05). No treatment-related fatalities were observed. This trial is registered with www.chictr.org.cn (ChiCTR2400081835) on 13 March 2024.