The most common treatment approach for patients with resectable pancreatic cancer is surgery, followed by six cycles of adjuvant chemotherapy with gemcitabine or, more recently, with gemcitabine/capecitabine in combination. Unfortunately, the majority of patients relapse within two years, highlighting a need for improved treatment options for early stage pancreatic cancer. At the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Thierry Conroy, MD (Lorraine Institute of Oncology, Lorraine, France), presented results from the international, randomized, phase III PRODIGE 24.CCTG PA.6 trial (N = 493), which compared a modified FOLFIRINOX regimen with no bolus fluorouracil (mFOLFIRINOX) to gemcitabine as adjuvant therapy for patients with resected pancreatic cancer. The primary endpoint was median disease-free survival (DFS).
At a median follow-up of 33.6 months, the median DFS was 21.6 months for patients receiving adjuvant mFOLFIRINOX, compared to 12.8 months for patients receiving gemcitabine (HR 0.58, P<.0001). The benefit of mFOLFIRINOX was observed in all prespecified patient subgroups. Median metastasis-free survival was 30.4 months with mFOLFIRINOX and 17.7 months with gemcitabine (HR 0.59, P<.0001). Treatment with mFOLFIRINOX also significantly improved overall survival (OS), from 35.0 months with gemcitabine to 54.4 months with mFOLFIRINOX (HR 0.64, P = .003).
In general, mFOLFIRINOX was more toxic than gemcitabine. The most common grade 3/4 adverse events (AEs) occurring in either treatment arm (mFOLIRINOX vs gemcitabine) were neutropenia. Of note, there was no difference among the treatment groups (28.4% vs 26.0%), likely due to use of secondary prophylaxis with GCSF in many patients in the FOLFIRINOX group (59.9% vs 3.7%). Rates of febrile neutropenia did not differ between the groups (2.9% vs 3.7%). Among nonhematologic AEs, FOLFIRINOX was related with more grade 3/4 diarrhea (18.6% vs 3.7%), fatigue (11% vs 4.6%), and sensory peripheral neuropathy (9.3% vs 0%). AEs observed with mFOLFIRINOX were manageable with dose delays and reductions. There were no treatment related deaths in FOLFIRINOX arm.
Dr Conroy concluded that mFOLFIRINOX is superior to gemcitabine as adjuvant therapy for resectable pancreatic cancer and should be considered the new standard of care in patients with good performance status. The discussant of this practice changing study, Colin Weekes, MD, PhD (Massachusetts General Hospital, Boston, Massachusetts, United States), agreed that this study represented a leap forward in management of resectable pancreatic cancer, but cautioned that these results are only applicable to otherwise healthy patients who are able to tolerate the toxicity of the mFOLFIRINOX regimen.