Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer

Marc Peeters, Timothy Jay Price, Andrés Cervantes, Alberto F. Sobrero, Michel Ducreux, Yevhen Hotko, Thierry André, Emily Chan, Florian Lordick, Cornelis J A Punt, Andrew H. Strickland, Gregory Wilson, Tudor Eliade Ciuleanu, Laslo Roman, Eric Van Cutsem, Valentina Tzekova, Simon Collins, Kelly S. Oliner, Alan Rong, Jennifer Gansert

Research output: Contribution to journalArticle

Abstract

Purpose: Panitumumab is a fully human anti - epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status. Patients and Methods: Patients with mCRC, one prior chemotherapy regimen for mCRC, Eastern Cooperative Oncology Group performance status 0 to 2, and available tumor tissue for biomarker testing were randomly assigned 1:1 to panitumumab 6.0 mg/kg plus FOLFIRI versus FOLFIRI every 2 weeks. The coprimary end points of PFS and overall survival (OS) were independently tested and prospectively analyzed by KRAS status. Results: From June 2006 to March 2008, 1,186 patients were randomly assigned 1:1 and received treatment. KRAS status was available for 91% of patients: 597 (55%) with wild-type (WT) KRAS tumors, and 486 (45%) with mutant (MT) KRAS tumors. In the WT KRAS subpopulation, when panitumumab was added to chemotherapy, a significant improvement in PFS was observed (hazard ratio [HR] = 0.73; 95% CI, 0.59 to 0.90; P = .004); median PFS was 5.9 months for panitumumab-FOLFIRI versus 3.9 months for FOLFIRI. A nonsignificant trend toward increased OS was observed; median OS was 14.5 months versus 12.5 months, respectively (HR = 0.85, 95% CI, 0.70 to 1.04; P = .12); response rate was improved to 35% versus 10% with the addition of panitumumab. In patients with MT KRAS, there was no difference in efficacy. Adverse event rates were generally comparable across arms with the exception of known toxicities associated with anti-EGFR therapy. Conclusion: Panitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS mCRC.

Original languageEnglish
Pages (from-to)4706-4713
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number31
DOIs
Publication statusPublished - Nov 1 2010

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Peeters, M., Price, T. J., Cervantes, A., Sobrero, A. F., Ducreux, M., Hotko, Y., André, T., Chan, E., Lordick, F., Punt, C. J. A., Strickland, A. H., Wilson, G., Ciuleanu, T. E., Roman, L., Van Cutsem, E., Tzekova, V., Collins, S., Oliner, K. S., Rong, A., & Gansert, J. (2010). Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. Journal of Clinical Oncology, 28(31), 4706-4713. https://doi.org/10.1200/JCO.2009.27.6055