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

<b>Background:</b> Niraparib is an oral poly (adenosine diphosphate-ribose) polymerase inhibitor with promising activity for patients with advanced breast cancer harboring germline <i>BRCA</i>1/2 mutations. <b>Methods:</b> 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 <i>BRCA</i>1/2 mutation (cohort A) or germline <i>BRCA</i>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. <b>Results:</b> 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. <b>Conclusions:</b> 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 <i>BRCA</i>1/2 mutations.