Neoadjuvant trio improves outcomes in locally advanced pancreatic cancer

  • Murphy JE & al.
  • JAMA Oncol
  • 30 May 2019

  • curated by Emily Willingham, PhD
  • Univadis Clinical Summaries
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Takeaway

  • phase 2 trial of total neoadjuvant therapy combining FOLFIRINOX and losartan followed by chemoradiotherapy (CRT) yields promising results, with 69% achieving R0 resection.

Why this matters

  • This patient population usually experiences poor outcomes, but preclinical data with drugs targeting the renin-angiotensin system, such as losartan, have suggested their antitumor potential.
  • A multicenter randomized phase 2 trial is underway.

Key results

  • 86% of patients (n=42) underwent surgery.
  • R0 resection was achieved in 34 of 49 patients (69%; 95% CI, 55%-82%).
  • Overall:
    • Median PFS: 17.5 (95% CI, 13.9-22.7) months.
    • Median OS: 31.4 (95% CI, 18.1-38.5) months.
  • Among those who had resection:
    • Median PFS: 21.3 (95% CI, 16.6-28.2) months.
    • Median OS: 33.0 (95% CI, 31.4 to not reached) months.
  • Adverse events: 
    • Most common (7 patients each): neutropenia, thrombocytopenia, diarrhea.
    • No single grade ≥3 in more than 14%.
    • Grades 3/4 all during FOLFIRINOX induction.
    • Grades 1/2 during CRT.

Study design

  • Phase 2 trial of 49 patients treated from August 22, 2013 to May 22, 2018.
  • FOLFIRINOX+losartan for 8 cycles.
  • Short- or long-course CRT.
  • Outcome: R0 resection rate.
  • Funding: NIH.

Limitations

  • Not randomized.