Unknown

Dataset Information

0

Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma.


ABSTRACT: PURPOSE:BRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC). METHODS:Patients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1-2 lines of treatment, Eastern Cooperative Oncology Group 0-2, were enrolled. Veliparib was dosed at a volume of 300 mg twice-daily (N = 3), then 400 mg twice-daily (N = 15) days 1-28. The primary end-point was to determine the response rate of veliparib; secondary end-points included progression-free survival (PFS), duration of response, overall survival (OS) and safety. RESULTS:Sixteen patients were enrolled; male N = 8 (50%). Median age was 52 years (range 43-77). Five (31%) had a BRCA1 and 11 (69%) had a BRCA2 mutation. Fourteen (88%) patients had received prior platinum-based therapy. No confirmed partial responses (PRs) were seen: one (6%) unconfirmed PR was observed at 4 months with disease progression (PD) at 6 months; four (25%) had stable disease (SD), whereas 11 (69%) had PD as best response including one with clinical PD. Median PFS was 1.7 months (95% confidence interval [CI] 1.57-1.83) and median OS was 3.1 months (95% CI 1.9-4.1). Six (38%) patients had grade III toxicity, including fatigue (N = 3), haematology (N = 2) and nausea (N = 1). CONCLUSIONS:Veliparib was well tolerated, but no confirmed response was observed although four (25%) patients remained on study with SD for ? 4 months. Additional strategies in this population are needed, and ongoing trials are evaluating PARPis combined with chemotherapy (NCT01585805) and as a maintenance strategy (NCT02184195).

SUBMITTER: Lowery MA 

PROVIDER: S-EPMC7351022 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications


<h4>Purpose</h4>BRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC).<h4>Methods</h4>Patients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1-2 lines of treatment, Eastern Cooperative Oncology Group 0-2, were enrolled. Veliparib was  ...[more]

Similar Datasets

| S-EPMC7193749 | biostudies-literature
| S-EPMC8133644 | biostudies-literature
| S-EPMC4292847 | biostudies-literature
| S-EPMC3725595 | biostudies-literature
| S-EPMC3227926 | biostudies-literature
| S-EPMC7376746 | biostudies-literature
| S-ECPF-MEXP-950 | biostudies-other
| S-EPMC4317401 | biostudies-other
| S-EPMC3805150 | biostudies-literature
| S-EPMC4453460 | biostudies-literature