Niraparib in pancreatic cancer with germline or somatic DNA damage repair (DDR) gene alterations (BRCA and beyond): a phase II study (NIRA-PANC).

Globally, pancreatic cancer is one of the leading causes of cancer-related mortality. Although FDA-approved chemotherapy regimens are available, rapid deterioration is often observed after first-line treatment. The PARP inhibitor niraparib may offer a therapeutic benefit in patients with advanced pancreatic cancer, necessitating thorough investigation. This was an open-label, single-arm, phase II trial involving 37 patients with metastatic or unresectable pancreatic cancer with DNA damage repair (DDR) gene alterations. Patients were administered niraparib (300 or 200 mg daily, based on weight and platelet count) in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal. Efficacy was assessed using the 6-month progression-free survival (PFS) rate as the primary endpoint. Of the 37 patients, 29 were evaluated for efficacy. The 6-month PFS rate was 41.38% (12/29 patients; 95% CI, 4.70%-100%), the median PFS was 4.4 months (95% CI, 3.6-6.5 months), and the median OS was 10.3 months (95% CI, 7.6-15.9 months). Further subgroup analysis revealed that the BRCA1/2 germline mutation-positive patient group (n = 14) reported a 6-month PFS rate of 50% and a median overall survival (mOS) of 12.1 months, while the non-BRCA group (n = 15) showed a 6-month PFS rate of 33.33% and a mOS of 10.3 months. Adverse events occurred in 78% of patients, the most common being anemia (27%), and no treatment-related deaths were observed. These data demonstrate clinical activity of niraparib in patients with metastatic or unresectable pancreatic cancers harboring DDR gene defects. Future studies are warranted to establish their roles in diverse genetic patient subpopulations. NCT03553004.