Gemcitabine has been the drug of choice for at least the past decade. But now, a new randomized phase III study presented at the 2018 ASCO (American Society of Clinical Oncology) annual meeting showed that a four-drug combination chemotherapy significantly improved survival compared with the standard regimen of single-agent gemcitabine for patients who underwent pancreatic cancer surgery.
Although adjuvant chemotherapy with gemcitabine has been an important option for patients, better drug approaches are needed, says gastrointestinal oncologist Dr. William T. Leslie of Rush University Medical Center in Chicago, Illinois, who was not involved in the new study. “We’ve been using gemcitabine postsurgery for about 10 years and it’s made a big difference for some patients, but not enough patients,” Leslie says. “I think that most of us are in agreement that this [new study] has set a potentially new standard of care for what we all know is an extraordinarily tough disease to treat.”
The problem, however, is the drug combo can be “very tough on patients in terms of side effects,” says Leslie, who is also an assistant professor of medicine.
What the Study Showed
The study name is PRODIGE 24/CCTG PA.6, and it was led by Thierry Conroy, M.D., a medical oncologist and director of the Institut de Cancerologie de Lorraine located in the French city of Nancy. The new regimen under investigation is mFOLFIRINOX, a modified combination containing oxaliplatin, leucovorin, irinotecan, and fluorouracil.
The study involved 493 patients with nonmetastatic pancreatic cancer who were treated at 77 French and Canadian centers from April 2012 to October 2016. Eligible patients must have undergone surgery and postoperative scans needed to show the tumor was completely removed—although microscopic tumor cells may still have been present. At three to 12 weeks after surgery, patients with good performance status were randomly assigned to receive either the standard gemcitabine regimen or the mFOLFIRINOX regimen for six months.
Improved Median Disease-Free Survival
- At a median follow-up of 33.6 months, the mFOLFIRINOX group had a median disease-free survival of 21.6 months vs 12.8 months for the gemcitabine group.
Improved Median Overall Survival
- The median overall survival also was higher: 54.4 months for the mFOLFIRINOX group versus 35.0 months for the gemcitabine group.
Improved Time until Metastases
- The mFOLFIRINOX group also had an extended time period until metastases (cancer spread) appeared. Median time until metastases with mFOLFIRINOX was 30.4 months vs 17.0 months with gemcitabine.
More Severe Side Effects
- The mFOLFIRINOX group did experience more severe side effects: 76 percent vs 53 percent.
Notable but Manageable Side Effects
“Yes, side effects can be managed, but I don’t want to minimize these side effects,” Leslie says, adding that side effects can include higher rates of diarrhea, fatigue, vomiting, mucositis (mouth and/or gut inflammation), and sensory peripheral neuropathy. “Patients will hear about this, and everyone will want it postsurgery. And it would be great if every patient would be a perfect candidate, but that’s not going to be the case. The regimen has more potential toxicities than gemcitabine alone, and not everyone will be able to handle it. What we need to do is find the right people for the regimen. And for those people, it could be remarkable.”
He emphasized that gemcitabine is still an important option for patients who have poor performance status scores postsurgery, and for those who have other medical conditions that make them poor candidates. “The data were very good, and it was a well-designed study,” Leslie says. “I’ve been at this a while, and patients need a win. This really is very welcome news.”