Adjuvant mFOLFIRINOX ‘new standard of care’ for pancreatic cancer
medwireNews: Adjuvant treatment with a modified (m)FOLFIRINOX regimen significantly improves survival relative to gemcitabine in patients with resected pancreatic ductal adenocarcinoma, according to findings presented at the ASCO Annual Meeting 2018, held in Chicago, Illinois, USA.
The benefits of adjuvant mFOLFIRINOX were seen for all endpoints and across all predefined subgroups, and although toxicities were worse with mFOLFIRINOX than with gemcitabine, they were manageable, said lead investigator Thierry Conroy, from the Institut de Cancérologie de Lorraine in Nancy, France.
As such, “mFOLFIRINOX should now be considered a new standard of care after pancreatic cancer resection in patients with good performance status, at least in Western countries,” he added.
The phase III PRODIGE 24/CCTG PA.6 trial included 493 patients with nonmetastatic disease who had undergone macroscopically complete resection (R0 or R1) at 77 centers in France or Canada. Participants were randomly assigned to receive mFOLFIRINOX – comprising fluorouracil 2.4 mg/m2 over 46 hours, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 plus irinotecan 150–180 mg/m2 – every 2 weeks for up to 12 cycles, or gemcitabine at a dose of 1000 mg/m2 every 3 or 4 weeks for a maximum of six cycles.
During a median follow-up of 33.6 months, median disease-free survival (DFS) was significantly improved for the 247 patients in the mFOLFIRINOX group relative to the 246 patients in the gemcitabine group, at 21.6 and 12.8 months, respectively, giving a hazard ratio (HR) of 0.58.
And the 3-year DFS rate was “almost doubled,” at 39.7% for mFOLFIRINOX versus 21.4% for gemcitabine, Conroy reported.
Overall survival and metastasis-free survival were also significantly longer with mFOLFIRINOX than with gemcitabine, at a median of 54.4 versus 35.0 months and 30.4 versus 17.7 months, respectively, with corresponding HRs of 0.64 and 0.59.
Improvements were also seen in pancreatic cancer-specific survival with mFOLFIRINOX, at a 3-year rate of 66.2% compared with 51.2% for gemcitabine (HR=0.63), a significant difference.
With regard to the adverse event (AE) profile, a number of nonhematologic AEs occurred significantly more often among mFOLFIRINOX- than gemcitabine-treated patients, including grade 3–4 diarrhea, fatigue, and sensory peripheral neuropathy. But the incidence of hematologic AEs of grade 3 or 4 was comparable across groups, except for thrombocytopenia, which occurred at a significantly higher rate in the gemcitabine study arm.
Conroy noted that the similar incidence of grade 3–4 neutropenia in both treatment arms was likely due to the significantly higher rate of secondary prophylaxis with granulocyte-colony stimulating factor in the mFOLFIRINOX group (59.9 vs 3.7%).
He also pointed out that although mFOLFIRINOX-treated participants were more likely to discontinue treatment prematurely due to toxicity or patient decision, the most common reason for discontinuation in the gemcitabine group was disease relapse.
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