Question

Describe evidence for use of PARP inhibitor in the management of patient with BRCAwt/HRD positive with recurrent high grade serous ovarian cancer.

Hint:

PARP inhibitors are effective not only for BRCA-mutated ovarian cancers but also for those with HRD, making them a promising treatment option for recurrent high-grade serous ovarian cancer.

Answer 1

PARP inhibitors have shown promising results in the management of recurrent high-grade serous ovarian cancer, especially in patients with homologous recombination deficiency (HRD), even in the absence of BRCA mutations.
Step 1: Evidence from Clinical Trials:
1. PRIMA Trial: As mentioned, niraparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer and HRD, even among those without BRCA mutations.
2. QUADRA Trial: A phase II trial evaluating the efficacy of niraparib in patients with recurrent ovarian cancer who had received multiple prior treatments. The study showed durable responses in patients with HRD-positive tumors, including those without BRCA mutations.
Step 2: Mechanism of Action:
PARP inhibitors target tumors with HRD by inhibiting the repair of single-strand DNA breaks, leading to double-strand breaks and ultimately cell death. This mechanism is effective in tumors with deficient DNA repair, regardless of BRCA status.