Patients with pancreatic cancer who underwent adjuvant chemotherapy with modified FOLFIRINOX had a median 20-month overall survival (OS) improvement compared with those treated with gemcitabine, results of the PRODIGE 24 trial found.
The improvement of median OS from 35.0 months with gemcitabine to 54.4 months with FOLFIRINOX represents a 36% reduction in the risk for death among patients assigned to the combination regimen (HR 0.64, 95% CI 0.48-0.86, P=0.003), reported researchers led by Thierry Conroy, MD, of l’Institut de Cancérologie de Lorraine, France, in the New England Journal of Medicine.
Significant improvements in the primary endpoint of median disease-free survival — 21.6 vs 12.8 months (HR 0.58, 95% CI 0.46-0.73, P<0.001) -- were also seen among patients assigned to modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin). However, these improvements in survival came at the expense of higher rates of adverse events, they noted.
In an editorial that accompanied the study, Hedy Kindler, MD, of the University of Chicago Medicine, wrote that the results represent the culmination of more than 10 years of work establishing FOLFIRINOX as a standard treatment for advanced pancreatic cancer.
“The remarkable results that have been achieved with adjuvant modified FOLFIRINOX therapy in the PRODIGE 24 trial have now changed the standard of care for many patients with resectable tumors,” Kindler wrote, noting that the median OS of 54.4 months is “truly unprecedented among patients with this disease.”
Pancreatic cancer is expected to become the second leading cause of cancer-related death in the U.S. in the next decade.
“Only about 20% of people, when found to have pancreatic cancer, are suitable for potentially curable surgical resection,” Robert Mayer, MD, of the Dana-Farber Cancer Institute in Boston, told MedPage Today when results of the study were first presented at the American Society of Clinical Oncology (ASCO) meeting earlier this year.
Even with resection, the majority of these patients will still experience disease recurrence. According to Mayer, there have been efforts in the last decades to try to give chemotherapy after surgical resection in the hope that the therapy enhances the likelihood of cure.
Data from the ESPAC-4 trial, presented at the 2016 ASCO meeting, showed that adjuvant gemcitabine plus capecitabine nearly doubled 5-year survival (28.8% vs 16.3%) in resectable pancreatic cancer compared with gemcitabine alone.
From 2012 to 2016 the phase III PRODIGE 24 trial randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive modified FOLFIRINOX or gemcitabine, the standard of care at study initiation.
Eligible patients were younger than age 80, had undergone R0 or R1 resection within 3 to 12 weeks, had a CA19-9 level of 180 U/mL or less, WHO performance status of 0 to 1, and adequate hematologic, liver, and renal function.
The median duration of follow-up was 33.6 months. Estimated disease-free survival at 3 years was 39.7% for FOLFIRINOX compared with 21.4% in the gemcitabine group, a difference Kindler called “impressive.”
Patients assigned to FOLFIRINOX also had significantly improved metastasis-free survival (30.4 vs 17.7 months, HR 0.59, 95% CI 0.46-0.75, P<0.001) and cancer-specific survival (not reached vs 36.4 months, HR 0.63, 95% CI 0.47-0.85, P=0.003) compared with patients assigned gemcitabine.
Three-quarters (75.9%) of the patients assigned FOLFIRINOX experienced grade 3 or 4 adverse events compared with about one-half (52.9%) of those in the gemcitabine group. One patient death occurred in the gemcitabine group because of treatment-related toxic effects. Patients assigned modified FOLFIRINOX had significantly higher rates of grade 3 or 4 diarrhea, increases in γ-glutamyltransferase levels, paresthesia, fatigue, sensory peripheral neuropathy, nausea, vomiting, abdominal pain, and mucositis.
Commenting on the toxicity of the regimen at ASCO, Vincent Chung, MD, of City of Hope in Duarte, Calif., told MedPage Today that it will be a challenge to select the best patients to tolerate this aggressive regimen.
“What we have seen with many types of cancer is that after surgical resections there are a lot of potential GI problems that occur, so they may not be able to complete chemotherapy regimens,” Chung said. “Being able to select the best patients is important.”
Conroy reported receiving travel support from Roche. Co-authors reported various ties to industry.
Kindler reported no relevant conflicts of interest but disclosed consultant fees from various companies.
Mayer disclosed relationships with Taiho Pharmaceutical and CASI Pharmaceuticals. Chung disclosed relationships with Celgene, Five Prime Therapeutics, Ipsen, and Perthera.