CHICAGO — A new standard of care has emerged for nonmetastatic pancreatic ductal adenocarcinoma (PDAC) in patients who have undergone surgical resection and have a good performance status.
In this patient group, the survival achieved with a modified FOLFIRINOX (mFOLFIRINOX) regimen (composed of oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil) achieved the best survival ever seen with any adjuvant treatment, say researchers presenting new results from a phase 3 study.
The median overall survival was 54.5 months with mFOLFIRINOX, compared with 35 months with gemcitabine; median disease-free survival was 21.6 months vs 12.8 months, respectively.
“For the first time, our trial shows a large benefit from adjuvant FOLFIRINOX chemotherapy over standard chemotherapy with gemcitabine,” said lead study author Thierry Conroy, MD, a medical oncologist and director of the Institut de Cancerologie de Lorraine in Nancy, one of the UNICANCER comprehensive cancer centers in France.
On the basis of these findings, “mFOLFIRINOX should now be considered a new standard of care after pancreatic cancer resection in patients with good performance status,” said Conroy. “The median survival with FOLFIRINOX is the best ever achieved with any adjuvant treatment, and there was a 15% increase in survival at 3 years.”
The new data were presented here at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting.
Noting that the results show a median overall survival of 4.5 years in pancreatic cancer, Richard Schilsky, MD, chief medical officer of ASCO, commented to Medscape Medical News: “We are just not used to talking about those sorts of numbers, so I consider this to be a big step forward in the management of patients with resectable cancer.”
“What we are seeing is an almost 2-year difference in survival, and that is pretty amazing,” given the general dismal prognosis of pancreatic cancer, commented Daniel Labow MD, system chief of surgical oncology at Mount Sinai and site chair of the Department of Surgery at Mount Sinai St. Luke’s and Mount Sinai West, New York City.
“This combination has already been proven to be more effective in the metastatic setting, and now we’re using it in the adjuvant setting, so it’s not surprising that we saw good results,” he told Medscape Medical News. “Of course, results don’t always translate from one setting to another, but in this case, we are seeing that.”
He predicts that it will change the standard of care for patients with resectable pancreatic cancer, but he pointed out that only about 20% of patients with pancreatic cancer ever make it to surgery. “So we are already taking patients who have a more favorable prognosis, and giving them a new and effective regimen, and what this is confirming — and in a positive way — that long-term survival is possible,” he said. “It’s all very encouraging, and the next step is if we can get more people to surgery by using FOLFIRINOX or another regimen.”
“This trial is basically confirmatory that the four-drug regimen and surgery can result in long-term survival, and this should be the standard of care in patients who can tolerate it,” Epstein added.
Superior for All Endpoints
Adjuvant chemotherapy is used to reduce the risk for recurrence in pancreatic cancer, and 6 months of gemcitabine and/or fluoropyrimidine has been the standard treatment in this setting since 2008, explained Conroy. “However, 71% to 76% of patients still relapse within 2 years despite these treatments, and there is an obvious need for a more efficient regimen to cure patients.”
FOLFIRINOX is more effective than gemcitabine in the metastatic setting, Conroy noted. “But as it could be too toxic for the adjuvant setting, a modified regimen was developed without the bolus of fluorouracil.”
The modified regimen is associated with less hematologic toxicities and diarrhea, but efficacy is not affected, he said.
In their multicenter study, Conroy and colleagues assessed the benefit of mFOLFIRINOX in the adjuvant setting in a cohort of 493 patients who were enrolled from 77 centers in France and Canada. All patients had undergone resection for nonmetastatic disease and were randomly assigned 21 to 84 days after surgery to receive gemcitabine (given in 28-day cycles on days 1, 8, and 15 for 6 cycles) or mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m² D1, and 5-fluoroucil 2.4 g/m² over 46 hours) every 14 days for 12 cycles.
At a median follow-up of 33.6 months, the median disease-free and overall survival durations were much longer in the mFOLFIRINOX group than in the gemcitabine group, as was metastasis-free survival (median, 30.4 months vs 17.0 months with gemcitabine; hazard ratio, 0.59).
The 3-year disease-free survival was also superior in the mFOLFIRINOX group compared with the gemcitabine group (39.7% vs 21.4%).
Similarly, 3-year overall survival was 63.4% vs 48.6% in favor of the combination regimen, and 3-year cancer specific survival was 66.2% vs 51.2%.
“The superiority of FOLFIRINOX was observed in all predefined patient subgroups,” said Conroy.
Grade 3/4 adverse events were more common in the mFOLFIRINOX group than in the gemcitabine group (76% vs 53%), including 12% with grade 4 events in each group. There was one treatment-related death in the gemcitabine group, and none in the mFOLFIRINOX group.
Conroy explained that the next step will be to explore the timing of chemotherapy and that mFOLFIRINOX appears to be a good candidate for neoadjuvant chemotherapy. Another option is to give it as perioperative chemotherapy; ongoing clinical trials are already investigating both of these approaches.
ASCO expert Andrew Epstein, MD, agreed with the authors that this does represent a new standard of care in this setting. “There was a significant improvement in survival for a notoriously aggressive disease,” he said, and he emphasized that it is important that this chemotherapy regimen is given to patients with a good performance status.
“It would be tempting to give this to anyone after surgery, but it is a relatively challenging regimen and we want to make sure we recommend it to patients who can withstand the rigorousness of this treatment,” said Epstein, who is an oncologist at Memorial Sloan Kettering Cancer Center in New York City. “This is one that I would recommend to my patients.”
American Society of Clinical Oncology (ASCO) 2018 Annual Meeting. Presented June 4, 2018. Abstract LBA4001
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A new standard of care has emerged for nonmetastatic pancreatic ductal adenocarcinoma (PDAC) in patients who have undergone surgical resection and have a good performance status. In this patient group, the survival achieved with a modified FOLFIRINOX (mFOLFIRINOX) regimen (composed of oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil) achieved the best survival ever seen with any adjuvant treatment, say researchers presenting new results from a phase 3 study.