TAPUR ( Targeted Agent and Profiling Utilization Registry ) is a phase II basket study evaluating anti-tumor activity of targeted agents in patients with advanced cancers with genomic alterations.
Results in a cohort of pancreatic cancer patients with germline or somatic BRCA1/2 inactivating mutations treated with Olaparib ( Lynparza ) are reported.
Eligible patients had advanced pancreatic cancer, no standard treatment options available, measurable disease, ECOG Performance Status ( PS ) 0-2, and adequate organ function.
Patients received Olaparib tablets or capsules dosed at 300 mg ( n=27 ) or 400 mg ( n=3 ), respectively, orally twice daily until disease progression.
Simon 2-stage design tested the null disease control ( DC ) ( objective response [ OR ] or stable disease at 16+ weeks [ SD16+ ] according to RECIST ) rate of 15% versus 35% ( power = 0.85; α = 0.10 ).
If 2 or more of 10 patients in stage 1 have disease control, 18 more patients are enrolled. If 7 or more of 28 patients have disease control, the standard treatment is worthy of further study.
Secondary endpoints are progression-free survival ( PFS ), overall survival ( OS ), and safety.
Thirty patients with BRCA1/2 inactivating mutations were enrolled in the period 2016-2019; 20 were previously treated with Platinum based therapy.
Two were not evaluable and excluded from efficacy analyses.
One partial response ( PR ) and 7 SD16+ were observed for disease control and objective response rates ( ORR ) of 31% ( 90% CI: 18% - 40% ) and 4% ( 95% CI: 0% - 18% ), respectively.
Seven patients had at least one grade 3 adverse effects or severe adverse effecs at least possibly related to Olaparib including anemia, diarrhea, fever, elevated liver enzymes, enterocolitis, increased bilirubin, and oral mucositis.
In conclusion, monotherapy Olaparib showed anti-tumor activity in heavily pre-treated patients with pancreatic cancer with germline ( 5/12 patients with objective response or SD16+ ) or somatic ( 3/16 patients with objective response or SD16+ ) BRCA1/2 inactivating mutations. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020