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


Authors: Lowery, M. A.; Kelsen, D. P.; Capanu, M.; Smith, S. C.; Lee, J. W.; Stadler, Z. K.; Moore, M. J.; Kindler, H. L.; Golan, T.; Segal, A.; Maynard, H.; Hollywood, E.; Moynahan, M.; Salo-Mullen, E. E.; Do, R. K. G.; Chen, A. P.; Yu, K. H.; Tang, L. H.; O'Reilly, E. M.
Article Title: 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). © 2017 Elsevier Ltd
Keywords: adult; clinical article; treatment response; aged; gene mutation; overall survival; constipation; disease course; fatigue; drug safety; side effect; cancer staging; germline; edema; progression free survival; phase 2 clinical trial; anemia; blood toxicity; nausea; thrombocytopenia; vomiting; dehydration; lymphocytopenia; tumor suppressor gene; hyponatremia; multicenter study; thromboembolism; pancreas adenocarcinoma; platinum; pancreatic cancer; brca; parp inhibitor; cisplatin derivative; veliparib; human; male; female; priority journal; article
Journal Title: European Journal of Cancer
Volume: 89
ISSN: 0959-8049
Publisher: Elsevier Inc.  
Date Published: 2018-01-01
Start Page: 19
End Page: 26
Language: English
DOI: 10.1016/j.ejca.2017.11.004
PROVIDER: scopus
PUBMED: 29223478
DOI/URL:
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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MSK Authors
  1. Zsofia Kinga Stadler
    144 Stadler
  2. Marinela Capanu
    206 Capanu
  3. Maeve Aine Lowery
    96 Lowery
  4. Kenneth Ho-Ming Yu
    58 Yu
  5. Kinh Gian Do
    112 Do
  6. Laura Hong Tang
    320 Tang
  7. Eileen O'Reilly
    316 O'Reilly
  8. David P Kelsen
    332 Kelsen
  9. Sloane Camille Baptiste Smith
    6 Smith
  10. Jonathan Wennan Lee
    2 Lee