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NORPACT-1

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1)

Phase 2N = 140NCT02919787

Population
Adults with WHO performance status 0-1 and a resectable pancreatic head tumour radiologically strongly suspected to be adenocarcinoma; 140 randomised (77 and 63).
Design
Multicentre, randomised phase 2 trial at 12 hospitals in Denmark, Finland, Norway and Sweden (ClinicalTrials.gov lists the study as phase 2/3). Randomised 3:2 before October 2018 and 1:1 afterwards to four cycles of neoadjuvant FOLFIRINOX then surgery and adjuvant chemotherapy, or upfront surgery then adjuvant chemotherapy. Adjuvant chemotherapy was initially gemcitabine plus capecitabine, with a later amendment permitting modified FOLFIRINOX. WHO performance status 0 or 1; resectable tumour of the pancreatic head. Not masked. Primary endpoint overall survival at 18 months. EudraCT 2015-001635-21.
Primary endpoint
Overall survival at 18 months
Arms
  • Upfront surgery (control, n = 63): Surgery followed by adjuvant chemotherapy
  • Neoadjuvant FOLFIRINOX (experimental, n = 77): Four cycles of FOLFIRINOX, then surgery and adjuvant chemotherapy
People
Labori KJ
Δ 18-month Overall survival at 18 months−13 pointsOSHR 1.52 (95% CI 1.00–2.33)Δ median OS−13.4 monthsOSHR 1.46 (95% CI 0.99–2.17)Δ median OS−11.4 monthsΔ Resection rate−7 points
Show the numbers
Results reported for NORPACT-1
EndpointAnalysisNeoadjuvant FOLFIRINOXUpfront surgeryEffect
Overall survival at 18 monthsprimaryLabori 202460% at 18 mo (49–71%)73% at 18 mo (62–84%)P=0.032Proportion alive at 18 months, intention to treat.
OSprimaryLabori 2024median 25.1 months (17.2–34.9)median 38.5 monthsHR 1.52 (95% CI 1.00–2.33)P=0.050The upfront-surgery median has a 95% CI of 27.6 to not reached, so no interval is recorded. A hazard ratio above 1 means a higher hazard of death in the neoadjuvant group. Log-rank p value as published. Median overall survival is reported alongside the 18-month primary endpoint.
OSPer-protocolexploratoryLabori 2024median 23 months (16.2–34.9)median 34.4 monthsHR 1.46 (95% CI 0.99–2.17)P=0.058Per-protocol population: 17 (22%) patients excluded from the neoadjuvant group and 8 (13%) from the upfront surgery group. The upfront-surgery median has a 95% CI of 19.4 to not reached, so no interval is recorded. The abstract does not label this analysis; 'exploratory' is the closest schema value.
Resection rateprimaryLabori 202482%89%P=0.2463 of 77 versus 56 of 63 patients.
Grade 3 or worse adverse eventsSafety population (73 neoadjuvant, 47 upfront surgery)primaryLabori 202458%40%42 of 73 versus 19 of 47 patients with at least one grade 3 or worse adverse event.
Results reported for NORPACT-1
EndpointAnalysisNeoadjuvant FOLFIRINOXUpfront surgeryEffect
Overall survival at 18 monthsprimaryLabori 202460% at 18 mo (49–71%)73% at 18 mo (62–84%)P=0.032Proportion alive at 18 months, intention to treat.
OSprimaryLabori 2024median 25.1 months (17.2–34.9)median 38.5 monthsHR 1.52 (95% CI 1.00–2.33)P=0.050The upfront-surgery median has a 95% CI of 27.6 to not reached, so no interval is recorded. A hazard ratio above 1 means a higher hazard of death in the neoadjuvant group. Log-rank p value as published. Median overall survival is reported alongside the 18-month primary endpoint.
OSPer-protocolexploratoryLabori 2024median 23 months (16.2–34.9)median 34.4 monthsHR 1.46 (95% CI 0.99–2.17)P=0.058Per-protocol population: 17 (22%) patients excluded from the neoadjuvant group and 8 (13%) from the upfront surgery group. The upfront-surgery median has a 95% CI of 19.4 to not reached, so no interval is recorded. The abstract does not label this analysis; 'exploratory' is the closest schema value.
Resection rateprimaryLabori 202482%89%P=0.2463 of 77 versus 56 of 63 patients.
Grade 3 or worse adverse eventsSafety population (73 neoadjuvant, 47 upfront surgery)primaryLabori 202458%40%42 of 73 versus 19 of 47 patients with at least one grade 3 or worse adverse event.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS1.521–2.33
OS1.460.99–2.17
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%020406080Months (modelled)
  • Neoadjuvant FOLFIRINOX (experimental)
  • Upfront surgery (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsNeoadjuvant FOLFIRINOXUpfront surgery
0100.0%100.0%
2451.5%64.9%
4826.6%42.1%
7213.7%27.4%
967.1%17.8%
Illustrative — modelled from reported values, not trial data. OS, exploratory.
0%25%50%75%100%020406080Months (modelled)
  • Neoadjuvant FOLFIRINOX (experimental)
  • Upfront surgery (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsNeoadjuvant FOLFIRINOXUpfront surgery
0100.0%100.0%
2251.5%64.2%
4327.4%42.0%
6514.1%27.0%
867.5%17.7%
Primary publication: Labori KJ, Bratlie SO, Andersson B, Angelsen JH, Biörserud C, Björnsson B, et al. Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024;9(3):205-217. PubMedDOI

Appears in

Sources

  1. Labori KJ, Bratlie SO, Andersson B, Angelsen JH, Biörserud C, Björnsson B, et al. Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024;9(3):205-217.

    PubMedDOI