Adjuvant mFOLFIRINOX extends OS by almost 20 months in pancreatic cancer
Adjuvant treatment with a modified FOLFIRINOX (mFOLFIRINOX) regimen extends overall survival (OS) by nearly 20 months compared with standard chemotherapy in patients with nonmetastatic pancreatic ductal adenocarcinoma (PDAC), results of a phase III trial have shown.
In the study, 493 patients with WHO performance status ≤1, adequate haematologic and renal function and no cardiac ischaemia were randomized to receive mFOLFIRINOX (oxaliplatin, leucovorin, irinotecan and 5-FU) or gemcitabine 21–84 days after R0 or R1 resection of PDAC. After a median follow-up of 33.6 months, median OS was 54.4 months in those receiving mFOLFIRINOX vs 35 months in those receiving gemcitabine. [Conroy T, et al, ASCO 2018, abstract LBA 4001]
“The median OS seen with mFOLFIRINOX is the longest ever achieved with any adjuvant treatment,” said investigator Dr Thierry Conroy of the Institut de Cancerologie de Lorraine in Nancy, France.
Disease-free survival (DFS), the primary endpoint of the study, was also much longer with mFOLFIRINOX vs gemcitabine (median, 21.6 months vs 12.8 months), as was metastasis-free survival (median, 30.4 months vs 17 months).
“The superiority of mFOLFIRINOX was observed in all predefined subgroup of patients,” Conroy reported. “At 3 years, the OS rate was 63.4 percent with mFOLFIRINOX vs 48.6 percent with gemcitabine, while the rate of cancer-specific survival was 66.2 percent vs 51.2 percent.”
“FOLFIRINOX was already shown to be more effective than gemcitabine in the metastatic setting. Based on the large benefit with adjuvant mFOLFIRINOX observed in our study, the regimen should now be considered a new standard of care after PDAC resection in patients with good performance status,” Conroy suggested.
In the study, grade 3/4 adverse events (AEs) occurred in 76 percent of patients treated with mFOLFIRINOX vs 53 percent of patients treated with gemcitabine, with 12 percent of patients experiencing grade 4 AEs in each group. There was one treatment-related death in the gemcitabine group vs 0 in the mFOLFIRINOX group.
Diarrhoea, nausea, vomiting and fatigue were more common in patients treated with mFOLFIRINOX, while patients treated with gemcitabine had higher rates of headache, fever, flu-like symptoms, swelling and low white blood cell counts. The risk of febrile neutropenia did not differ significantly between the two groups.
“The next step will be to explore the timing of chemotherapy. mFOLFIRINOX appears to be a good candidate for neoadjuvant chemotherapy and perioperative chemotherapy. Ongoing trials are evaluating these approaches in pancreatic cancer,” said Conroy.
Despite the long-term survival benefit reported with adjuvant mFOLFIRINOX in this study, only about 10–20 percent of patients with pancreatic cancer are candidates for surgery. Further research is needed to identify strategies that can improve the dismal prognosis of patients.