Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer.

Abstract

BACKGROUND:

The study 20050181 demonstrated significant improvements in progression-free survival (PFS), objective response, and a nonsignificant trend toward increased overall survival (OS) with panitumumab-FOLFIRI versus FOLFIRI alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Updated long-term data from a prespecified descriptive analysis are reported.

PATIENTS AND METHODS:

Patients receiving one prior mCRC treatment were randomly assigned (1:1) to panitumumab (6.0 mg/kg)-FOLFIRI versus FOLFIRI every 2 weeks. Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS status.

RESULTS:

One thousand one hundred and eighty-six patients were randomly assigned. In patients with WT KRAS tumors, panitumumab-FOLFIRI significantly improved PFS versus FOLFIRI [median 6.7 versus 4.9 months; hazard ratio (HR) 0.82 [95% confidence interval (CI) 0.69, 0.97]; P = 0.023]. A trend toward longer OS was observed (median 14.5 versus 12.5 months; HR 0.92 [95% CI 0.78, 1.10]; P = 0.37). Response rates improved from 10% to 36% (P < 0.0001). From post hoc analyses in patients receiving prior oxaliplatin-bevacizumab, panitumumab-FOLFIRI improved PFS (median 6.4 versus 3.7 months; HR 0.58 [95% CI 0.37, 0.90]; P = 0.014). PFS and OS appeared longer for worst-grade skin toxicity of 2-4, versus 0-1 or FOLFIRI. Safety results were as previously reported and consistent with the known toxicities with anti-epidermal growth factor receptor therapy.

CONCLUSIONS:

These data confirm the primary efficacy and safety findings of this trial and support panitumumab-FOLFIRI as a second-line treatment of WT KRAS mCRC.

• Authors: M Peeters, T J Price, A Cervantes, A F Sobrero, M Ducreux, Y Hotko, T André, E Chan, F Lordick, C J A Punt, A H Strickland, G Wilson, T E Ciuleanu, L Roman, E Van Cutsem, Y Tian, R Sidhu
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 25 Issue 1 Pg. 107-16 (Jan 2014) ISSN: 1569-8041 [Electronic] England
• PMID: 24356622 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Panitumumab
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (adverse effects, analogs & derivatives, therapeutic use)
• Colorectal Neoplasms (drug therapy, mortality, pathology)
• Disease-Free Survival
• Female
• Fluorouracil (adverse effects, therapeutic use)
• Humans
• Kaplan-Meier Estimate
• Leucovorin (adverse effects, therapeutic use)
• Liver Neoplasms (drug therapy, mortality, secondary)
• Male
• Middle Aged
• Panitumumab
• Quality of Life
• Skin Diseases (chemically induced)
• Treatment Outcome