Adjuvant chemotherapy with a modified dose of FOLFIRINOX (mFOLFIRINOX) was associated with significantly better survival outcomes, particularly disease-free survival (DFS) and overall survival (OS), compared with single-agent gemcitabine in patients with resected pancreatic ductal adenocarcinoma (PDAC), according to a 5-year analysis of the PRODIGE 24/Canadian Cancer Trials Group PA6* study.
This multicentre (77 hospitals in France and Canada), open-label, phase III trial involved 493 patients (mean age 62.0 years, 43.8 percent female) with PDAC who underwent complete macroscopic (R0/R1) resection. Participants were randomly assigned to receive either adjuvant mFOLFIRINOX** (n=247) or gemcitabine*** (n=246). [JAMA Oncol 2022;doi:10.1001/jamaoncol.2022.3829]
At a median follow-up of 69.7 months, median DFS was significantly longer among those treated with mFOLFIRINOX compared with gemcitabine (21.4 vs 12.8 months; stratified hazard ratio [HR], 0.66, 95 percent confidence interval [CI], 0.54–0.82; p<0.001).
Patients on mFOLFIRINOX also had a significantly longer median OS than those on gemcitabine (53.5 months vs 35.5 months; p=0.001).
“Noticeably, the gain in DFS with treatment with mFOLFIRINOX translate[d] into an OS benefit, with a 32 percent risk reduction in the risk of death compared with the gemcitabine group,” said the researchers.
Five-year DFS and OS rates were higher in the mFOLFIRINOX group vs the gemcitabine group (26.1 percent vs 19.0 percent [DFS] and 43.2 percent vs 31.4 percent [OS]).
In addition, fewer deaths occurred in the mFOLFIRINOX group than the gemcitabine group (44.7 percent vs 55.3 percent).
Significantly prolonged median metastasis-free survival (29.4 vs 17.7 months; stratified HR, 0.64, 95 percent CI, 0.52–0.80; p<0.001) and cancer-specific survival (54.7 vs 36.3 months; stratified HR, 0.65, 95 percent CI, 0.51–0.82; p<0.001) were observed in patients treated with mFOLFIRINOX compared with gemcitabine.
In a multivariable analysis, adjuvant chemotherapy with mFOLFIRINOX (HR, 0.65; p<0.001), age <70 years (HR, 0.70; p=0.02), well-differentiated tumour grade (HR, 0.69; p=0.01), and tumour stages of IA/IIB, IIA, and IIIB (HRs, 0.10, 0.24, and 0.35, respectively; p=0.002 for all) were factors significantly associated with improved OS.
However, a shorter time from the end of adjuvant therapy to disease relapse was considered an adverse prognostic factor for OS (HR 1.03; p<0.001). Therefore, it is important to facilitate early detection and treatment of relapse, the researchers noted.
No new safety signals were observed with this longer follow-up.
“This final 5-year analysis with mature data … indicates that adjuvant chemotherapy with a mFOLFIRINOX regimen significantly prolonged DFS, OS, metastasis-free survival, and cancer-specific survival compared with treatment with gemcitabine,” said the researchers.
“These findings confirm treatment with mFOLFIRINOX as the recommended adjuvant regimen [following PDAC resection],” they added.
*PRODIGE 24/Canadian Cancer Trials Group PA6: Trial comparing adjuvant chemotherapy with gemcitabine versus mFOLFIRINOX to treat resected pancreatic adenocarcinoma
**oxaliplatin 85 mg/m², irinotecan 150–180 mg/m², leucovorin 400 mg/m², and fluorouracil 2,400 mg/m² every 2 weeks for 12 cycles
***gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 28 days for six cycles