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The PRIME Study: Panitumumab with Infusional Fluorouracil, Leucovorin and Oxaliplatin (FOLFOX4) versus FOLFOX Alone
Background

Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody is currently approved by the Food and Drug Administration (FDA) in the metastatic colorectal cancer (mCRC) setting as a single agent. There is great interest in the study of this agent in combination with chemotherapy.

Douillard et al report on the results of the PRIME study, a multicenter, open-label randomized phase III trial in a recent issue of the Journal of Clinical Oncology. 
  • The study enrolled 1,183 patients from among 133 institutions in 19 countries
    • 1,096 of these patients (93%) had KRAS results available
      • 60% was wild type (WT) KRAS
      • 40% mutated (MT) KRAS
The study was designed to compare the effect of panitumumab plus infusional chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as a first-line treatment for mCRC in patients with WT KRAS tumors.

Patients were randomly assigned 1:1 to either panitumumab-FOLFOX4 or FOLFOX4 alone.  
  • The primary end point was progression-free survival (PFS)
  • The secondary endpoint was overall survival (OS)

Results

The PRIME data demonstrates that panitumumab in combination with FOLFOX4 is well tolerated and significantly improved PFS in patients with WT KRAS tumors.

  • WT KRAS patients, receiving panitumumab-FOLFOX4 significantly improved PFS compared with patients receiving FOLFOX4 alone
    • Median PFS, 9.6 versus 8.0 months, respectively (hazard ratio [HR], 0.90, 95% confidence interval [CI], 0.66 to 0.97; P = .02).
    • A favorable increase in OS was observed, although it was statistically nonsignificant (panitumumab-FOLFOX4 versus FOLFOX4 (23.9 months versus 19.7 months respectively.
  • MT KRAS patients, the panitumumab-FOLFOX4 arm showed a PFS significantly reduced versus the FOLFOX4 alone patients (HR, 1.29, 95% CI, 1.04 to 1.62; P = .02)
    • Median OS of 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068) 

All of the planned subsets demonstrated favorable effects of panitumumab on PFS with the exception of three groups:  

  • Patients > 65 years of age
  • Women
  • Patients with an ECOG performance status of 2
    • However a favorable OS effect was noted in women and older patients receiving panitumumab 
    • Increased skin toxicity was observed in patients receiving panitumumab, with an association seen between skin toxicity and efficacy

ManageCRC.com Commentary

The PRIME trial demonstrates the activity of panitumumab in combination with FOLFOX in first-line therapy of mCRC, adding to the body of literature on the role of EGFR antibodies in the treatment of this common disease.  

  • The National Comprehensive Cancer Network (NCCN) guidelines concur and have listed panitumumab or cetuximab as possible options when considering anti-EGFR therapy and chemotherapy in the first and second-line treatment setting of mCRC.2
    • This is in contrast to the current Food and Drug Administration (FDA) indication for panitumumab, which calls for this agent to be administered as monotherapy on or after the failure of multiple chemotherapy agents.
    • For cetuximab, the FDA approval is as a single agent after failure of multiple chemotherapy agents or in combination with irinotecan.
    • Additionally, based on retrospective analysis, both of these agents are restricted to use in KRAS WT patients.
  •  Oncology nurses can take away from this trial
    • There are two EGFR antibodies, panitumumab and cetuximab, with activity in mCRC in combination with chemotherapy.
    • The side effect profile of panitumumab is similar to cetuximab;
      • Infusion reactions are less common with panitumumab
      • Panitumumab two-week treatment schedule is favorable

References

  1. Douillard J-Y, Siena S, Cassidy J et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME Study. J Clin Oncol. 2010;29:1-11. doi:10.1200/JCO.2009.27.4860 Link to abstract http://jco.ascopubs.org/content/early/2010/10/01/JCO.2009.27.4860.abstract 
  2. National Comprehensive Cancer Network (NCCN). The NCCN Guidelines for Colon Cancer: v.1.0 2011. Retrieved from www.nccn.org.


Article Created On : 11/12/2010 2:21:39 PM             Article Updated On : 11/12/2010 2:21:39 PM