PRODIGE 24
FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer (PRODIGE 24 / Canadian Cancer Trials Group PA6)
Phase 3N = 493NCT01526135
- Population
- Adults aged 18 to 79 with resected (R0/R1) pancreatic ductal adenocarcinoma; 493 randomised.
- Design
- Open-label randomised phase 3 trial at 77 hospitals in France and Canada (5-year report). Patients aged 18 to 79 with histologically confirmed pancreatic ductal adenocarcinoma and complete macroscopic (R0/R1) resection 3 to 12 weeks before randomisation were randomised 1:1 to modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2 reduced to 150 mg/m2 after a protocol-specified safety analysis, leucovorin 400 mg/m2, fluorouracil 2400 mg/m2, every 2 weeks) or gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 4 weeks, for 24 weeks. Primary endpoint disease-free survival; overall survival secondary. Inclusion April 2012 to October 2016. EudraCT 2011-002026-52.
- Primary endpoint
- DFS
- Arms
- Gemcitabine (control): Gemcitabine 1000 mg/m2 days 1, 8, 15 every 4 weeks for 24 weeks
- Modified FOLFIRINOX (experimental): Oxaliplatin, irinotecan, leucovorin and fluorouracil every 2 weeks for 24 weeks
- People
- Conroy T, PRODIGE 24 / CCTG PA6
DFSHR 0.58 (95% CI 0.46–0.73)Δ median DFS+8.8 monthsΔ 36-month DFS+18.3 pointsOSHR 0.64 (95% CI 0.48–0.86)Δ median OS+19.4 monthsΔ 36-month OS+14.8 points
Show the numbers
| Endpoint | Analysis | Modified FOLFIRINOX | Gemcitabine | Effect |
|---|---|---|---|---|
| DFSRandomised patients (493); analysis population not labelled in the abstract | primarymedian follow-up 33.6 monthsConroy 2018 | median 21.6 months; 39.7% at 3 y | median 12.8 months; 21.4% at 3 y | HR 0.58 (95% CI 0.46–0.73)P<0.001Stratified hazard ratio for cancer-related event, second cancer, or death. |
| OSRandomised patients (493); analysis population not labelled in the abstract | primarymedian follow-up 33.6 monthsConroy 2018 | median 54.4 months; 63.4% at 3 y | median 35 months; 48.6% at 3 y | HR 0.64 (95% CI 0.48–0.86)P=0.003Secondary endpoint, reported with the primary DFS analysis; stratified hazard ratio for death. |
| Grade 3 or 4 adverse eventsRandomised patients (493); safety population not labelled in the abstract | primaryConroy 2018 | 75.9% | 52.9% | One patient in the gemcitabine group died from toxic effects (interstitial pneumonitis). |
| DFSRandomised patients (493); analysis population not labelled in the abstract | finalmedian follow-up 69.7 monthsConroy 2022 | median 21.4 months (17.5–26.7); 26.1% at 5 y | median 12.8 months (11.6–15.2); 19% at 5 y | HR 0.66 (95% CI 0.54–0.82)P< .001The authors describe the 5-year report as the final results of the trial. |
| OSRandomised patients (493); analysis population not labelled in the abstract | finalmedian follow-up 69.7 monthsConroy 2022 | median 53.5 months (43.5–58.4); 43.2% at 5 y | median 35.5 months (30.1–40.3); 31.4% at 5 y | HR 0.68 (95% CI 0.54–0.85)P=.001The authors describe the 5-year report as the final results of the trial. |
| Endpoint | Analysis | Modified FOLFIRINOX | Gemcitabine | Effect |
|---|---|---|---|---|
| DFSRandomised patients (493); analysis population not labelled in the abstract | primarymedian follow-up 33.6 monthsConroy 2018 | median 21.6 months; 39.7% at 3 y | median 12.8 months; 21.4% at 3 y | HR 0.58 (95% CI 0.46–0.73)P<0.001Stratified hazard ratio for cancer-related event, second cancer, or death. |
| OSRandomised patients (493); analysis population not labelled in the abstract | primarymedian follow-up 33.6 monthsConroy 2018 | median 54.4 months; 63.4% at 3 y | median 35 months; 48.6% at 3 y | HR 0.64 (95% CI 0.48–0.86)P=0.003Secondary endpoint, reported with the primary DFS analysis; stratified hazard ratio for death. |
| Grade 3 or 4 adverse eventsRandomised patients (493); safety population not labelled in the abstract | primaryConroy 2018 | 75.9% | 52.9% | One patient in the gemcitabine group died from toxic effects (interstitial pneumonitis). |
| DFSRandomised patients (493); analysis population not labelled in the abstract | finalmedian follow-up 69.7 monthsConroy 2022 | median 21.4 months (17.5–26.7); 26.1% at 5 y | median 12.8 months (11.6–15.2); 19% at 5 y | HR 0.66 (95% CI 0.54–0.82)P< .001The authors describe the 5-year report as the final results of the trial. |
| OSRandomised patients (493); analysis population not labelled in the abstract | finalmedian follow-up 69.7 monthsConroy 2022 | median 53.5 months (43.5–58.4); 43.2% at 5 y | median 35.5 months (30.1–40.3); 31.4% at 5 y | HR 0.68 (95% CI 0.54–0.85)P=.001The authors describe the 5-year report as the final results of the trial. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.58 | 0.46–0.73 |
| OS | 0.64 | 0.48–0.86 |
| DFS | 0.66 | 0.54–0.82 |
| OS | 0.68 | 0.54–0.85 |
- Modified FOLFIRINOX (experimental)
- Gemcitabine (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Modified FOLFIRINOX | Gemcitabine |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 14 | 63.8% | 46.9% |
| 27 | 42.0% | 23.2% |
| 41 | 26.8% | 10.9% |
| 54 | 17.7% | 5.4% |
- Modified FOLFIRINOX (experimental)
- Gemcitabine (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Modified FOLFIRINOX | Gemcitabine |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 34 | 64.8% | 51.0% |
| 68 | 42.0% | 26.0% |
| 102 | 27.3% | 13.3% |
| 136 | 17.7% | 6.8% |
Appears in
Sources
Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018;379(25):2395-2406.
Conroy T, Castan F, Lopez A, Turpin A, Ben Abdelghani M, Wei AC, et al. Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial. JAMA Oncol. 2022;8(11):1571-1578.