Personalized medicine comes to PDAC

  • Rainone M & al.
  • JAMA Oncol
  • 13 Feb 2020

  • curated by Jim Kling
  • Univadis Clinical Summaries
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Takeaway

  • A review calls for more frequent testing of germline mutations in patients with pancreatic ductal adenocarcinoma (PDAC), as well as more research to identify therapeutic targets.

Why this matters

  • Almost 1 in 10 patients with PDAC has an actionable germline mutation.

Key points

  • Several recent data sets have shown evidence of pathogenic germline alterations (PGAs), at a frequency of about 10%.
    • Most common are BRCA1, BRCA2, and ATM.
    • Least common include PALB2, MLH1, MSH2, MSH6, PMS2, CDKN2A, and TP53.
    • Aggregate frequencies range from 3.8% to 9.7%.
  • BRCA1/2 mutations identified in 3%-7% of patients with PDAC.
  • The American Society of Clinical Oncology and the National Comprehensive Cancer Network now recommend assessing all patients with PDAC for PGAs, even without a family history or ethnic factors.
  • Treatment options influenced by PGAs include:
    • Checkpoint inhibitor therapy for mismatch repair-deficient and microsatellite instability PDAC.
    • Poly-ADP (adenosine diphosphate)-ribose polymerase (i.e., PARP) inhibitor therapy as a maintenance approach and platinum therapy for BRCA1/2 and PALB2 PDAC.