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FOLFIRINOX improved OS in metastatic pancreatic adenocarcinoma
Combination therapy extended median OS to 11.1 months in patients with good performance status.
First-line treatment with the FOLFIRINOX regimen for metastatic pancreatic adenocarcinoma in patients with a good performance status significantly improved OS, PFS, response rate and time to degradation of quality of life compared with gemcitabine, according to the phase 3 results of the PRODIGE 4/ACCORD 11 trial.
“This is the first time in a phase 3 randomized study that we achieved an 11-month median survival for metastatic pancreatic cancer,” said Thierry Conroy, MD, of the Centre Alexis Vautrin, Vandoeuvre les Nancy, France, who presented the results of this analysis at the 2010 ASCO Annual Meeting in Chicago.
“We recommend FOLFIRINOX (5-FU, leucovorin, irinotecan and oxaliplatin) as the new international standard of care for patients with metastatic pancreatic cancer, but only in patients with normal levels of bilirubin and performance status of zero to one,” Conroy said.
Improved outcomes
The trial enrolled 342 patients between 2005 and October 2009. Patients were all chemotherapy-naive, aged 18 to 75 years (median 61 years), and had histologically/cytologically confirmed metastatic pancreatic adenocarcinoma. In addition, all patients had to have a performance status of zero or one.
The patients were randomly assigned gemcitabine or FOLFIRINOX. They were stratified by center, performance status and tumor location.
The preplanned interim analysis was conducted by an independent data monitoring committee in September. At this time, it recommended to stop the study.
Data indicated that patients on the FOLFIRINOX regimen had improved response (31.6% vs. 9.4%; P=.0001) and improved disease control (70.2% vs. 50.9%; P=.0003) compared with gemcitabine.
In addition, FOLFIRINOX significantly extended the median PFS (6.4 months vs. 3.3 months; P<.0001) and OS (11.1 months vs. 6.8 months; P<.0001) compared with gemcitabine.
“There was also a large difference in the time to definitive quality-of-life degradation in favor of the FOLFIRINOX arm,” Conroy said.
Adverse events
One toxic death occurred in each treatment arm. In addition, patients on FOLFIRINOX had higher rates of grade-3/4 febrile neutropenia (5.4% vs. 0.6%) than patients on gemcitabine.
Patients on gemcitabine had higher levels of alanine aminotransferase (18.6% vs. 7.3%).
These results “emphasize the need for vigilant patient selection, education, monitoring and active management,” Conroy said. “FOLFIRINOX is more toxic but overall has manageable toxicities.” – by Leah Lawrence
These data may be practice-changing in terms of establishing a new chemotherapy regimen as front-line treatment of metastatic pancreatic cancer, using a non-gemcitabine-based regimen. It is the most positive phase 3 study we have ever seen in advanced pancreatic cancer, with an absolute improvement in median survival of 4.3 months compared to single-agent gemcitabine. Compared with prior phase 3 studies, the overwhelming majority of which have been negative, these data are too striking to ignore.
Of concern, however, is the tolerability and toxicity of this elaborate multidrug regimen. It is certainly only applicable for good performance status patients. Moving forward, providers will certainly want to gain some personal experience using this regimen to confirm that it is safe and tolerable in our patient population. I don't anticipate we will see a whole-sale switch away from gemcitabine-based regimens immediately.
– Andrew Ko, MD
HemOnc Today Editorial Board member
For more information:
- Conroy T. #4010. Presented at: the 2010 ASCO Annual Meeting; June 4-8; Chicago.
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