ACCORD 11 and MPACT Trials

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The ACCORD 11 trial (NCT00000620), published in 2011, revolutionized pancreatic cancer treatment by establishing FOLFIRINOX as superior to single-agent gemcitabine for advanced disease. This French phase 3 randomized trial included patients 75 years or younger with excellent performance status (ECOG 0-1), adequate organ function, and no prior chemotherapy. FOLFIRINOX demonstrated significant improvements in overall survival (HR 0.57) and progression-free survival (HR 0.47), establishing it as standard care for fit, young patients with metastatic pancreatic adenocarcinoma.

However, FOLFIRINOX’s significant toxicity profile, including diarrhea, cytopenia, anorexia, and fatigue, led to widespread adoption of modified FOLFIRINOX regimens in clinical practice. Most institutions implemented dose reductions, particularly reducing irinotecan from 180 mg/m² to 150 mg/m² while maintaining oxaliplatin at 85 mg/m², leucovorin at 400 mg/m², and continuous 5-fluorouracil at 2400 mg/m². Importantly, no formal noninferiority trial has validated modified FOLFIRINOX compared with the original regimen.

The MPACT trial (NCT00844649) in 2013 addressed the need for more broadly applicable treatment options by comparing gemcitabine plus nab-paclitaxel vs gemcitabine alone. This study included a more diverse patient population with Karnofsky performance status of greater than or equal to 70, no age restrictions, and 41% of patients aged 65 years or older. Despite the broader eligibility criteria, the trial met its primary end point with improved overall survival (HR 0.72) and progression-free survival, establishing gemcitabine plus nab-paclitaxel as another standard first-line option for advanced pancreatic cancer.