Every person is different; every situation is different; every cancer is different. So, the decision about which treatment is right for an individual patient with pancreatic cancer (ductal adenocarcinoma of the pancreas) by their health care team is highly complex. Here we present the work of published research that examines factors related to two of the most common chemotherapy regimens in use for advanced stage pancreatic cancer.
A December 2016 study in the World Journal of Gastroenterology by Kattan et al. compared information from the phase III clinical trial reported out in the New England Journal of Medicine article in 2011 that measured the 4-drug FOLFIRINOX regimen favorably against the use of gemcitabine alone in metastatic pancreatic cancer WITH information from the phase III clinical trial reported out in the New England Journal of Medicine article in 2013 that measured gemcitabine plus Abraxane favorably against the use of gemcitabine alone in metastatic pancreatic cancer. The authors addressed such topics as study design, efficacy, toxicity, effects on quality of life, and the cost effectiveness of these two regimens, based on these two key studies.
TRIAL DESIGN
In general, patients with pancreatic cancer who received FOLFIRINOX were somewhat younger and more robust, on balance, than those from the gemcitabine + Abraxane trial (the FOLFIRINOX study used ECOG standards, and the gemcitabine + Abraxane study used Karnofsky measures). These factors could have skewed the results in the latter trial to more side effects and toward reduced clinical response rates. This is a very important point to keep in mind in considering these studies.
Characteristic FOLFIRINOX G + Abraxane
Duration 2005 – 2009 2009 – 2012
# Patients 171 431
Location France multinational
Age, min-med-max 25-61-76 27-62-86
Performance status 37-62-1 16-77-7
EFFICACY
The FOLFIRINOX study in regard to its cohort appeared to show better efficacy in comparison to the pancreatic cancer patient cohort in the gemcitabine + Abraxane study. This latter study included patients from North America, Australia, and Eastern and Western Europe. A subgroup analysis of Canadians in this study demonstrated an overall pancreatic cancer survival duration of 11.9 months, pointing to possible outcome differences between countries involved.
Characteristic FOLFIRINOX G + Abraxane
Overall Response Rate 31.6% 23%
PR 31% 23%
SD 38.6% 27%
DCR 70.2% 48%
PFS1/2 (mos) 6.4 5.5
OS1/2 (mos) 11.1 8.5
1-yr Overall Survival 48.4% 35%
TOXICITY & QUALITY of LIFE
For the first two months of treatment, the FOLFIRINOX study seemed to show improved overall patient health status by relieving several pancreatic cancer symptoms (except diarrhea). The Gemcitabine + Abraxane study did not assess quality of life, but the regimen appeared to improve quality-adjusted survival in metastatic pancreatic cancer compared to the use of gemcitabine alone.
Adverse Event FOLFIRINOX G +Abraxane
Neutropenia 45.7% 38%
Thrombocytopenia 9.1% 13%
Anemia 7.8% 13%
Fatigue 23.6% 17%
Peripheral Neuropathy 9% 17%
Diarrhea 12.7% 6%
Alopecia (grade 2) 11.4% 50%
COST
Here we use 2014 Medicare average sales prices for the three pancreatic cancer treatment regimens. The bottom row assumes that patients continued until progression per key study results (each with their own unique demographics). The UK’s National Health Service has rejected Abraxane due to cost.
Cost Gemcitabine FOLFIRINOX G + Abraxane
Monthly Cost $1,363 $7,234 $12,221
PFS1/2 (mos) 3.7 6.4 5.5
Cost to progression $5,043 $46,298 $67,216
SUMMARY
Both FOLFIRINOX and Gemcitabine plus Abraxane improve the duration of survival compared to gemcitabine, which had been the standard of care for advanced pancreatic cancer. It is difficult to compare these drug regimens as the patient populations are different and, to date, no study has done a direct comparison in pancreatic cancer. But this idea of comparing the Phase III clinical trial results of the two treatment regimens is a very clever one by Kattan and colleagues. Until more direct data are available, one has the sense from comparisons such as this, that FOLFIRINOX may offer slightly better efficacy, with comparable or possibly slightly more intense side effects. But direct comparative data are not yet available. So, as Paul Simon says, we are left with “hints and allegations” until that time. The costs of these regimens for advanced pancreatic cancer are surprisingly high.
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David Dessert