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
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Mary Ellen Moynahan
    104 Moynahan
  2. Zsofia Kinga Stadler
    202 Stadler
  3. Marinela Capanu
    256 Capanu
  4. Maeve Aine Lowery
    128 Lowery
  5. Kenneth Ho-Ming Yu
    97 Yu
  6. Kinh Gian Do
    142 Do
  7. Laura Hong Tang
    353 Tang
  8. Eileen O'Reilly
    424 O'Reilly
  9. David P Kelsen
    428 Kelsen
  10. Sloane Camille Baptiste Smith
    6 Smith
  11. Jonathan Wennan Lee
    2 Lee