A Phase II Trial of Niraparib in Patients with Advanced Pancreatic Cancer Harboring Pathogenic Variants in ATM , BRCA1 , BRCA2 , PALB2 , and CHEK2

作者：Brandon M. Huffman, Miklós Dióssy, Matthew B.B. Yurgelun, Nora Horick, Yvonne Y. Li, J. Crowdis, Huy Nguyen, Kalindi T Parmar, Bose S. Kochupurakkal, Leonard Vonk, Helen Lam, Kaitlyn Ramsey, Elizabeth Andrews, Sarah C. Loeb, Leigh Culnane, Leah H. Biller, Andrea J. Bullock, Andrea Catherine Enzinger, Marios Giannakis, Nadine A. Jackson, Kimmie Ng, Jonathan Andrew Nowak, Anuj Kishor Patel, Kimberly Perez, Ahmed Rattani, Douglas Adam Rubinson, Benjamin L. Schlechter, Harshabad Singh, Mingyang Cai, Srivatsan Raghavan, Jefferey W. Clark, Mary Linton Peters, Caroline M. Weipert, Brian Matthew Wolpin, Alan D D'Andrea, Geoffrey I. Shapiro, Andrew J. Aguirre, Zoltán Szállási, James M. Cleary · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1078-0432.ccr-24-3766 · 被引用次数：2 · 研究领域：PARP inhibition in cancer therapy、Sirtuins and Resveratrol in Medicine、Cancer Research and Treatments

PURPOSE: PARP inhibition has demonstrated efficacy in patients with platinum-sensitive pancreatic cancer with germline BRCA1/2 pathogenic variants (PV). Whether PARP inhibitors might be effective in a broader population of patients with pancreatic cancer remains under investigation. PATIENTS AND METHODS: This multicenter, open-label phase II trial (NCT03601923) enrolled patients with advanced pancreatic cancers who harbored germline or somatic BRCA1, BRCA2, PALB2, ATM, and/or CHEK2 PVs. Patients with prior progression on platinum-based therapy were excluded. Patients were treated with niraparib 200 or 300 mg once daily, with their initial dose determined by weight and platelet count. The primary endpoint was 6-month progression-free survival (PFS). RESULTS: Thirty-two patients [10 women (31%); median age: 67 years] were enrolled. Patients had a PV in at least one of the following genes: ATM (n = 14), BRCA2 (n = 10), PALB2 (n = 3), CHEK2 (n = 4), or BRCA1 (n = 2). The 6-month PFS was 25% [90% confidence interval (CI), 13%-41%] for the overall population, exceeding the preestablished threshold of 17%. The median PFS for the entire population was 2 months (95% CI, 1.4-3.8), and the objective response rate was 14% (95% CI, 4%-33%). All six patients with ≥6 months of PFS and evaluable tumor zygosity had biallelic inactivation of a DNA repair gene. Three patients with biallelic inactivation of ATM and no progression on prior chemotherapy received niraparib for more than 1 year. CON...