Breast cancer is the most common cause of cancer death in women worldwide. Defects in the DNA damage response pathway has been identified as an underlying cause of breast cancer. Specifically, a homologous recombination deficiency (HRD) can cause the body to be unable to repair double strand breaks in DNA, thereby making it harder for cancer cells to repair themselves. Additionally, the risk of developing breast cancer substantially increases when there is a germline mutation in the BRCA gene, which produces proteins that help repair damaged DNA. In fact, it is estimated that 5% of HR+/HER- breast cancer patients harbor a germline BRCA mutation and 10-20% of HR+/HER- breast cancer patients have a homologous recombination deficiency.
Poly(ADP-ribose)polymerase (PARP) inhibition has been explored as an novel approach to cause cell death in tumor cells that harbor deficiencies in DNA-repair mechanisms and patterns of genomic stability. Niraparib, is a potent, orally active PARP 1/2 inhibitor that has demonstrated activity in breast cancer patients. Currently, there is a phase III study evaluating niraparib as a second-line therapy for germline BRCA mutated (gBRCAm) HER- advanced breast cancer.
MEDSIR’s LUZERN trial is a multi-center, phase II trial evaluating the efficacy and safety of niraparib combined with aromatase inhibitors for either gBRCAm or germline BRCA wildtype (gBRCAwt) with HRD HR+/HER- metastatic breast cancer. The study is divided into two cohorts: Cohort A, patients with gBRCAm, and Cohort B, patients with gBRCAwt HRD. The primary endpoint is the clinical benefit ratio in each cohort. In addition, the study will explore the presence of BRCA mutations and HRD in patients with metastatic breast cancer, as well as evaluate if there are any predictive/prognostic biomarkers and identify any mechanisms of resistance.
The study is recruiting 23 patients in 10 sites across Spain and is supported by GlaxoSmithKline (GSK).
Contact us if you want to learn more about this trial or have an idea for your own investigator-initiated trial!