Pembrolizumab monotherapy for previously treated metastatic HER2-negative breast cancer with germline <i>APOBEC3B</i> deletion: results of the phase II AUROR study.
prospective_cohort · Level II
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- Record sourced from PubMed, PMID 40697533.
- Also identified by DOI 10.1016/j.lanwpc.2025.101637 and PMC identifier 12281068.
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Abstract
A common germline deletion polymorphism in the <i>APOBEC3B</i> gene increases the rate of somatic hypermutation in breast cancer, which in turn is associated with greater neoantigen burden and immune activation. This phase II study evaluated the impact of the <i>APOBEC3B</i> deletion polymorphism on the response to pembrolizumab monotherapy in metastatic HER2-negative breast cancer patients. Eligible patients had a confirmed diagnosis of metastatic HER2-negative breast cancer, 1-3 prior lines of therapy, and documented homozygous or heterozygous germline deletion of <i>APOBEC3B</i>. Patients received 200 mg of pembrolizumab intravenously every 3 weeks for up to 2 years. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression-free survival, and overall survival. <b>Clinical trial registration:</b>ClinicalTrials.gov, NCT03989089. All enrolled patients (N = 44) were women, 30% (12/40) had PD-L1-positive tumours, and 64% (28/44) had received ≥2 previous lines of therapy for metastatic disease. Objective response rate (ORR) was 20% (9/44) (95% CI, 9.8-35.3) in the total and 25% (3/12) (95% CI, 5.5-57.2) in the PD-L1-positive population. Disease control rate (DCR) for the study was 52% (23/44) (95% CI, 36.7-67.5). Median progression-free survival (PFS) was 3.1 months (95% CI, 2.1-4.3), and 6-month PFS rate was 27% (12/44) (95% CI, 16.8-44.2). Median overall survival (OS) was 15.5 months (95% CI, 13.0-26.5), and 12-month OS rate was 66% (29/44) (95% CI, 53.3-82.5). Treatment-related adverse events (AEs) occurred in 30 (68%) patients, including 1 (2%) with a grade 3 AE. There were no deaths due to AEs. Pembrolizumab monotherapy demonstrated anti-tumour activity in a subset of previously treated metastatic HER2-breast cancer patients with germline <i>APOBEC3B</i> deletion. This study was sponsored by Cancer Research Malaysia, a non-profit cancer research organization. Merck Sharp & Dohme (MSD) provided free access to the trial drug through the Merck Investigator Studies Program.