Olaparib in Patients With Pancreatic Cancer With BRCA1/2 Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study

PURPOSE Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with advanced pancreatic cancer with BRCA1/ 2 mutations treated with olaparib are reported. METHODS Eligible patients had advanced pancreatic cancer, measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options available. Genomic testing was performed in Clinical Laboratory Improvement Amendments–certified, College of American Pathologists-accredited site selected laboratories. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16 weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of stable disease, and safety. RESULTS Thirty patients with BRCA1/ 2 mutations were enrolled from November 2016 to August 2019. The median number of reported previous therapies was 3 (range, 1-10). Two patients were not evaluable and excluded from efficacy analyses. Two patients with complete response, three with partial response and three with SD16+, were observed for DC and OR rates of 31% (90% CI, 18 to 40; P = .04) and 18% (95% CI, 6 to 37), respectively. The median PFS was 8 (95% CI, 8 to 15) weeks, and the median OS was 38 (95% CI, 21 to 65) weeks. Three patients had at least one drug-related grade 3 adverse event or serious adverse event of anemia, fever, or oral mucositis. CONCLUSION Olaparib showed antitumor activity in patients with advanced pancreatic cancer with BRCA1/ 2 mutations extending findings of recent studies of olaparib in patients with this disease.