PREOPANC-2
Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2)
Phase 3N = 375
- Population
- Adults with resectable or borderline resectable pancreatic ductal adenocarcinoma and WHO performance status 0-1; 375 randomised, 369 in the modified intention-to-treat population.
- Design
- Investigator-initiated, open-label, nationwide phase 3 randomised trial in 19 Dutch centres. Randomised 1:1 (minimisation, stratified by resectability and centre) to neoadjuvant FOLFIRINOX for eight cycles then surgery without adjuvant treatment, or three cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) in the second cycle, then surgery and four cycles of adjuvant gemcitabine. WHO performance status 0 or 1. Primary endpoint overall survival in the modified intention-to-treat population (ineligible patients excluded). Registered with EudraCT 2017-002036-17 per the abstract; no ClinicalTrials.gov number is printed and none was found by search.
- Primary endpoint
- OS
- Arms
- Neoadjuvant gemcitabine-based chemoradiotherapy (control, n = 187): Three cycles of gemcitabine with 36 Gy in 15 fractions in cycle two, then surgery and four cycles of adjuvant gemcitabine
- Neoadjuvant FOLFIRINOX (experimental, n = 188): Eight cycles of FOLFIRINOX, then surgery without adjuvant treatment
- People
- Janssen QP
OSHR 0.88 (95% CI 0.69–1.13)Δ median OS+0.6 monthsΔ Grade 3 or worse adverse events+7 points
Show the numbers
| Endpoint | Analysis | Neoadjuvant FOLFIRINOX | Neoadjuvant gemcitabine-based chemoradiotherapy | Effect |
|---|---|---|---|---|
| OSModified intention-to-treat (369 of 375; four ineligible patients and two who withdrew consent immediately were excluded) | primarymedian follow-up 42.3 monthsJanssen 2025 | median 21.9 months (17.7–27.0) | median 21.3 months (16.8–25.5) | HR 0.88 (95% CI 0.69–1.13)P=0.32 |
| Grade 3 or worse adverse eventsPatients assessed for adverse events (175 FOLFIRINOX, 176 chemoradiotherapy; denominators from the neutropenia counts in the abstract, consistent with 117 = 67% and 106 = 60%) | primaryJanssen 2025 | 67% | 60% | P=0.20117 versus 106 patients. The most common grade 3-4 events in the FOLFIRINOX and chemoradiotherapy groups were neutropenia (25% vs 22%), diarrhoea (23% vs 1%) and leukopenia (8% vs 15%). Treatment-related deaths: 2 (1%) vs 1 (1%). |
| Endpoint | Analysis | Neoadjuvant FOLFIRINOX | Neoadjuvant gemcitabine-based chemoradiotherapy | Effect |
|---|---|---|---|---|
| OSModified intention-to-treat (369 of 375; four ineligible patients and two who withdrew consent immediately were excluded) | primarymedian follow-up 42.3 monthsJanssen 2025 | median 21.9 months (17.7–27.0) | median 21.3 months (16.8–25.5) | HR 0.88 (95% CI 0.69–1.13)P=0.32 |
| Grade 3 or worse adverse eventsPatients assessed for adverse events (175 FOLFIRINOX, 176 chemoradiotherapy; denominators from the neutropenia counts in the abstract, consistent with 117 = 67% and 106 = 60%) | primaryJanssen 2025 | 67% | 60% | P=0.20117 versus 106 patients. The most common grade 3-4 events in the FOLFIRINOX and chemoradiotherapy groups were neutropenia (25% vs 22%), diarrhoea (23% vs 1%) and leukopenia (8% vs 15%). Treatment-related deaths: 2 (1%) vs 1 (1%). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.88 | 0.69–1.13 |
- Neoadjuvant FOLFIRINOX (experimental)
- Neoadjuvant gemcitabine-based chemoradiotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Neoadjuvant FOLFIRINOX | Neoadjuvant gemcitabine-based chemoradiotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 14 | 64.2% | 63.4% |
| 27 | 42.5% | 41.5% |
| 41 | 27.3% | 26.3% |
| 55 | 17.5% | 16.7% |
Appears in
Sources
Janssen QP, van Dam JL, van Bekkum ML, Bonsing BA, Bos H, Bosscha KP, et al. Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial. Lancet Oncol. 2025;26(10):1346-1356.