Final results from PRIME: Randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer

Jean Yves Douillard, S. Siena, J. Cassidy, J. Tabernero, R. Burkes, M. Barugel, Y. Humblet, G. Bodoky, D. Cunningham, J. Jassem, F. Rivera, I. Kocákova, P. Ruff, M. Błasińska-Morawiec, M. Šmakal, J. L. Canon, M. Rother, K. S. Oliner, Y. Tian, F. XuR. Sidhu

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Abstract

Background: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. Patients and methods: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. Results: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) forWT KRAS mCRC was 23.9 months (95%CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P=0.17 (68%OS events). An exploratory analysis of updated survival (>80%OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95%CI 0.70-0.98; P=0.03 forWT KRASmCRC. The adverse event profile was consistent with the primary analysis. Conclusions: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.

Original languageEnglish
Article numbermdu141
Pages (from-to)1346-1355
Number of pages10
JournalAnnals of Oncology
Volume25
Issue number7
DOIs
Publication statusPublished - Jul 2014

Keywords

  • Antibody
  • Chemotherapy
  • FOLFOX
  • Metastatic colorectal cancer
  • Panitumumab

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Douillard, J. Y., Siena, S., Cassidy, J., Tabernero, J., Burkes, R., Barugel, M., Humblet, Y., Bodoky, G., Cunningham, D., Jassem, J., Rivera, F., Kocákova, I., Ruff, P., Błasińska-Morawiec, M., Šmakal, M., Canon, J. L., Rother, M., Oliner, K. S., Tian, Y., ... Sidhu, R. (2014). Final results from PRIME: Randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Annals of Oncology, 25(7), 1346-1355. [mdu141]. https://doi.org/10.1093/annonc/mdu141