In PDAC with BRCA/PALB2 mutations, a potential standard treatment

  • O'Reilly EM & al.
  • J Clin Oncol
  • 24 Jan 2020

  • curated by Jim Kling
  • Univadis Clinical Summaries
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Takeaway

  • Cisplatin+gemcitabine (CG) showed good efficacy in pancreatic ductal adenocarcinoma (PDAC) with BRCA/PALB2 mutations, and veliparib offered no additional response rate advantage but led to more hematological toxicity.

Why this matters

  • The authors suggest that CG should be the standard approach for untreated PDAC.

Study design

  • Open-label, randomized, multicenter, phase 2 study (n=50).
  • Patients with untreated germline BRCA/PALB2 mutations with stage III-IV PDAC were randomized to CG or CG with veliparib (CG+V).
  • Funding: NIH and nonindustry sources.

Key results

  • The response rate was 65.2% for CG and 74.1% for CG+V (P=.55), both of which exceeded the prespecified activity threshold.
  • Disease control rate, 78.3% for CG and 100% for CG+V (P=.02).
  • Median PFS: for CG, 9.7 vs 10.1 months for CG+V (P=.73).
  • Median OS: for CG, 16.4 vs 15.5 months for CG+V (P=.6).
  • Overall OS:
    • 2-year, 30.6% (95% CI, 17.8%-44.4%).
    • 3-year, 17.8% (95% CI, 8.1%-30.7%).
  • Grade 3-4 hematologic toxicities, CG vs CG+V:
    • neutropenia, 30% vs 48%;
    • thrombocytopenia, 9% vs 55%; and
    • anemia, 35% vs 52%.

Limitations

  • Small sample size, open-label design.