This phase II cohort from the Targeted Agent and Profiling Utilization Registry (TAPUR) study evaluated the clinical activity of olaparib in patients with advanced pancreatic cancer harboring BRCA1/2 mutations who had progressed following standard treatment options. A total of 30 patients were enrolled between November 2016 and August 2019, with 28 being evaluable for efficacy. The study used Simon’s two-stage design with a primary endpoint of disease control (DC), defined as objective response (complete or partial) or stable disease lasting ≥16 weeks (SD16+). Patients were treated with olaparib either as tablets (600 mg daily) or capsules (800 mg daily) until disease progression or unacceptable toxicity.
The median number of prior systemic therapies was three (range, 1–10), and 70% had received prior platinum-based chemotherapy. Among the 28 evaluable patients, olaparib demonstrated a disease control rate of 31% (90% CI, 18 to 40; P = 0.04) and an objective response rate of 18%, including two complete responses, three partial responses, and three cases of prolonged stable disease. The median progression-free survival was 8 weeks, and the median overall survival was 38 weeks. Most patients who benefited had BRCA2 mutations, suggesting a potentially stronger correlation between BRCA2 alterations and PARP inhibitor sensitivity in pancreatic cancer. Importantly, responses were observed regardless of platinum sensitivity, further supporting olaparib’s potential utility in later lines of therapy.
Olaparib was well-tolerated overall, with only three patients (10%) experiencing grade 3 treatment-related adverse events, including anemia, fever, and oral mucositis. No grade 4 or 5 adverse events were reported. These findings add to existing evidence from prior trials such as POLO and studies of other PARP inhibitors like rucaparib, and suggest olaparib may provide meaningful benefit in patients with BRCA-mutated pancreatic cancer beyond the maintenance setting. Furthermore, this study supports the need to explore olaparib earlier in the treatment course and to assess its benefit in patients with both germline and somatic BRCA mutations, as well as those with other homologous recombination repair gene alterations.
