In fit patients with metastatic pancreatic adenocarcinoma, does first-line FOLFIRINOX improve survival compared with gemcitabine alone? [PRODIGE 4/ACCORD 11]
In fit patients with metastatic pancreatic adenocarcinoma, does first-line FOLFIRINOX improve survival compared with gemcitabine alone?
Absolute Effect
Median OS was 11.1 vs 6.8 months; HR 0.57 (95% CI 0.45–0.73), P<.001. One-year OS was 48.4% vs 20.6%.
Absolute effect: At 1 year, survival improved by 27.8 percentage points (48.4% vs 20.6%). Median PFS was 6.4 vs 3.3 months; HR 0.47, P<.001. Response rate was 31.6% vs 9.4%.
NNT: 4, based on 1-year overall survival (absolute improvement 27.8 percentage points).
NNH: 5, based on grade 3–4 neutropenia (45.7% vs 21.0%; absolute increase approximately 24.7 percentage points).
Follow-up: Median follow-up 26.6 months.
Clinical results and treatment burden
- Intervention: FOLFIRINOX every 2 weeks: oxaliplatin 85 mg/m², irinotecan 180 mg/m², leucovorin 400 mg/m² and 5-FU 400 mg/m² bolus followed by 2,400 mg/m² over 46 h, versus gemcitabine 1,000 mg/m² on the standard weekly schedule.
- Principal toxicity: FOLFIRINOX caused substantially more grade 3–4 toxicities, particularly neutropenia, febrile neutropenia and diarrhea. Febrile neutropenia occurred in 5.4%.
- Other efficacy/recurrence findings: Quality-of-life deterioration at 6 months occurred in 31% vs 66%, favouring FOLFIRINOX despite greater treatment toxicity.
- Quality of life: Time to definitive deterioration of QoL was significantly delayed with FOLFIRINOX (HR 0.47, 95% CI 0.30–0.70; P<.001).
Eligibility and clinical context
342 chemotherapy-naïve patients with metastatic pancreatic adenocarcinoma, ECOG performance status 0–1 and adequate organ function; patients ≥76 years were excluded.
Limitations and maturity: The trial enrolled a selected fit population and therefore does not establish FOLFIRINOX as the default for frail, elderly or ECOG ≥2 patients. Subsequent modified regimens may have different toxicity.