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Adjuvant FOLFIRINOX new standard of care for pancreatic cancer
CHICAGO — Adjuvant FOLFIRINOX chemotherapy improved OS and PFS compared with gemcitabine among patients with surgically removed nonmetastatic pancreatic ductal adenocarcinoma, according to data from the phase 3 PRODIGE 24/CCTG PA.6 trial presented at ASCO Annual Meeting.
“The FOLFIRINOX regimen should now be considered a new standard of care after pancreatic resection in patients with good performance status,” Thierry Conroy, MD, medical oncologist and director of the Institut de Cancerologie de Lorraine in France, said during a press conference.
For the past decade, 6 months of gemcitabine has been the standard adjuvant therapy after resection for pancreatic cancer. However, between 71% and 76% of patients relapse within 2 years.
FOLFIRINOX — composed of oxaliplatin, leucovorin, irinotecan and 5-FU — has been shown to be more effective than gemcitabine in the first-line setting for patients with metastatic pancreatic cancer with good performance status. However, its role in the adjuvant setting was unknown.
Researchers enrolled patients in France and Canada with nonmetastatic pancreatic ductal adenocarcinoma who underwent surgery for tumor removal. Within 3 months after surgery, researchers randomly assigned 493 patients to gemcitabine or FOLFIRINOX for 6 months.
DFS served as the primary outcome; secondary outcomes included OS, toxicity and specific-survival.
Median follow-up was 33.6 months.
Results showed median DFS was 21.6 months with FOLFIRINOX vs. 12.8 months with gemcitabine (HR = 0.58; 95% CI, 0.46-0.73).
Median OS was 54.4 months with FOLFIRINOX vs. 35 months with gemcitabine (HR = 0.64; 95% CI, 0.48-0.86). Time to metastases also was extended with FOLFIRINOX (median, 30.4 months vs. 17 months).
Researchers observed significantly more serious adverse events with FOLFIRINOX (76% vs. 30%). The most common treatment-related adverse events included diarrhea (18.6% vs. 3.7%), fatigue (11% vs. 4.6%) and sensory peripheral neuropathy (9.3% vs. 0). Of note, there was one treatment-related death in the gemcitabine arm and no deaths in the FOLFIRINIX arm.
“As expected, the FOLFIRINOX regimen is more toxic than gemcitabine, but it is a safe regimen with manageable toxicities” Conroy said. – by Jennifer Southall
Reference:
Conroy T, et al. LBA4001. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Conroy reports travel accommodations or expenses from Roche. Please see the abstract for all other author’s relevant financial disclosures.
Perspective
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This trial demonstrates better efficacy of modified FOLFIRINOX compared with gemcitabine as adjuvant therapy for previously resected pancreatic adenocarcinoma. The trial reached its intended endpoint and showed improved OS in the experimental arm with quite impressive median survival of 54.4 months.
The control arm of the study gemcitabine alone is no longer recognized as the standard of care since the release of the ESPAC4 trial in the U.K., which showed a 28-month median OS in gemcitabine plus capecitabine arm. In ESPAC-4, the control arm of gemcitabine showed inferior survival of only 25.5 months, which may be due to the differences in the patient populations, including the percentage of patients with positive margins who apparently did not benefit much from the gemcitabine plus capecitabine regimen in the subset analysis of ESPAC-4.
It will be very interesting to understand the factors contributing to such impressive results in the FOLFIRINOX arm, which is an undoubtedly a very effective, albeit toxic, chemotherapy regimen. In the U.S., many centers follow the strategy of maximizing neoadjuvant therapy due to understanding of pancreatic cancer as of a systemic disease. This also helps avoiding unnecessary surgeries and surgeries with positive margins where no therapy provides appreciable survival benefit. Considering the results of the study by Conroy and colleagues, this trial is impressive and confirmatory of FOLFIRINOX being a very effective chemotherapy regimen now applicable in the adjuvant setting for resected pancreatic cancer.
Reference:
Neoptolemos JP, et al. Lancet. 2017;doi:10.1016/S0140-6736(16)32409-6.
Perspective
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This is a very important potential new standard of care for patients with resectable pancreatic cancer because of the significant improvement in survival outcomes. The challenge will be the delivery of this regimen to patients after they undergo the extensive surgery required for pancreatic cancer. Patients are debilitated after surgery, and it is hard to get in a regimen such as FOLFIRINOX, but it can be done.
The median survival improvement of 54 months vs. 35 months with gemcitabine alone is the most we have seen in a long time. I was surprised this presentation was not included in the plenary session because of the significance of the data in this disease, where outcomes are so poor. This is an extremely important survival improvement that is very encouraging news for patients able to have surgery.
The other thing to keep in mind, however, is the comparator arm was gemcitabine alone and we have not used gemcitabine alone as adjuvant therapy for many years now. The standard of care today is gemcitabine plus capecitabine.
We now need to figure out how we can get more patients to surgery so they can be treated with this new treatment regimen. FOLFIRINOX should become the new standard of care following resection among patients with pancreatic cancer. However, the application of the regimen may be difficult, so we need to think about this in our patient subgroups, because not all patients will be able to handle such a regimen. I also would now like to see what the response is for patients with BRCA mutations in pancreatic cancer using FOLFIRINOX in the adjuvant setting.
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