- A 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.
- 86% of patients (n=42) underwent surgery.
- R0 resection was achieved in 34 of 49 patients (69%; 95% CI, 55%-82%).
- 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.
- 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.
- Not randomized.