Niraparib Plus Aromatase Inhibitors for Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer with a Germline Mutation.

Niraparib is an oral poly (adenosine diphosphate-ribose) polymerase inhibitor with promising activity for patients with advanced breast cancer harboring germline 1/2 mutations. LUZERN (NCT04240106) was a multicenter, open-label, Simon's two-stage, phase II clinical trial evaluating the efficacy and safety of niraparib with aromatase inhibitors (AIs) for patients with HR-positive/HER2-negative advanced breast cancer with either a germline 1/2 mutation (cohort A) or germline 1/2 wild-type and homologous recombination deficiency (exploratory cohort B). Eligible patients received ≤1 line of chemotherapy and 1-2 prior lines of endocrine therapy for advanced disease with secondary resistance to the last AI-based regimen. Patients received niraparib (300 mg or 200 mg) plus an AI. The primary endpoint was the clinical benefit rate (CBR) in cohort A. Between June 2020 and November 2022, 14 patients were enrolled in cohort A (n = 6 for stage I, n = 8 for stage II) and no patients were enrolled in cohort B. One patient was excluded from the efficacy analysis due to no prior AI treatment. Nearly all patients (92.9%) previously received a cyclin-dependent kinase 4/6 inhibitor, but no patients had received prior platinum-based chemotherapy. Median follow-up was 16.7 months (range: 13.2-18.2). The CBR was 46.2% (95% CI: 19.2-74.9), meeting the primary endpoint. Median progression-free survival was 5.5 months (95% CI: 1.9-8.5), and median overall survival was 18.1 months (95% CI: 9.7-NE). The safety profile was consistent with the known toxicity of both drugs. Niraparib combined with an AI has encouraging antitumor activity and a manageable safety profile in patients with AI-resistant HR-positive/HER2-negative advanced breast cancer with germline 1/2 mutations.