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

Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Maeve A. Lowery, David P. Kelsen, Marinela Capanu, Sloane C. Smith, Jonathan W. Lee, Zsofia K. Stadler, Malcolm J. Moore, Hedy L. Kindler, Talia Golan, Amiel Segal, Hannah Maynard, Ellen Hollywood, MaryEllen Moynahan, Erin E. Salo-Mullen, Richard Kinh Gian Do, Alice P. Chen, Kenneth H. Yu, Laura H. Tang, Eileen M. O'Reilly
PurposeBRCA-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).MethodsPatients 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.ResultsSixteen 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).ConclusionsVeliparib 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).



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