As reported in JAMA Oncology by Thierry Conroy, MD, and colleagues, 5-year analysis of the phase III PRODIGE 24/Canadian Cancer Trials Group PA6 trial has shown a significant benefit in overall survival and other outcomes with adjuvant mFOLFIRINOX (modified oxaliplatin, irinotecan, leucovorin, and fluorouracil) vs gemcitabine in patients with pancreatic ductal adenocarcinoma. Results at 3 years showed a significant benefit in the primary endpoint of disease-free survival.
Thierry Conroy, MD
In the open-label trial, 493 patients who underwent R0/R1 resection at sites in France and Canada were randomly assigned between April 2012 and October 2016 to receive mFOLFIRINOX (n = 247) or gemcitabine (n = 246). Treatment consisted of 24 weeks of oxaliplatin at 85 mg/m2, irinotecan at 150 to 180 mg/m2, leucovorin at 400 mg/m2, and fluorouracil at 2,400 mg/m2 every 2 weeks; or gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks.
Key Findings
Median follow-up in the current analysis was 69.7 months (95% confidence interval [CI] = 67.1–73.9 months). Median disease-free survival was 21.4 months (95% CI = 17.5–26.7 months) in the mFOLFIRINOX group vs 12.8 months (95% CI = 11.6–15.2 months) in the gemcitabine group (hazard ratio [HR] = 0.66, 95% CI = 0.54–0.82, P < .001). Rates at 5 years were 26.1% vs 19.0%.
Median overall survival was 53.5 months (95% CI = 43.5–58.4 months) vs 35.5 months (95% CI = 30.1–40.3 months), with a hazard ratio of 0.68 (95% CI = 0.54–0.85, P = .001). Rates at 5 years were 43.2% vs 31.4%.
Median metastasis-free survival was 29.4 months (95% CI = 21.4–40.1 months) vs 17.7 months (95% CI = 14.0–21.2 months), with a hazard ratio of 0.64 (95% CI = 0.52–0.80, P < .001). Median cancer-specific survival was 54.7 months (95% CI = 45.8–68.4 months) vs 36.3 months (95% CI = 30.5–43.9 months), with a hazard ratio of 0.65 (95% CI = 0.51–0.82, P < .001).
At relapse, chemotherapy was received by 107 (66.9%) of 160 patients in the mFOLFIRINOX group, with 72 (67.3%) receiving a gemcitabine-based regimen, and by 151 (83.0%) of 182 in the gemcitabine group, with 112 (74.2%) receiving FOLFIRINOX. Median postrelapse overall survival was 13.1 months (95% CI = 10.4–18.3 months) vs 15.0 months (95% CI = 12.3–18.4 months).
On multivariate analysis, factors significantly associated with improved overall survival were random assignment to mFOLFIRINOX (HR = 0.65, P < .001), age < 70 years (HR = 0.70, P = .02), tumor grade of well-differentiated tumors (HR = 0.69, P = .01), tumor staging (HRs of 0.10, 0.24, and 0.35, overall P = .002, for IA/IB, IIA, and IIB vs III/IV, respectively), and treatment at centers including ≥ 10 study patients (HR = 0.77, P = .03). Shorter time from end of adjuvant therapy to disease relapse was associated with poorer overall survival after relapse (HR = 1.03, P < .001).
The investigators concluded, “The final 5-year results from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial indicate that adjuvant treatment with modified FOLFIRINOX yields significantly longer survival than gemcitabine in patients with resected pancreatic ductal adenocarcinoma.”
Dr. Conroy, of the Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by R&D Unicancer, French Ministry of Health and the Institut National du Cancer, French National League against Cancer, Canadian Cancer Society, and 7 Days in May. For full disclosures of the study authors, visit jamanetwork.com.
